US6083524A - Polymerizable biodegradable polymers including carbonate or dioxanone linkages - Google Patents
Polymerizable biodegradable polymers including carbonate or dioxanone linkages Download PDFInfo
- Publication number
- US6083524A US6083524A US08/944,739 US94473997A US6083524A US 6083524 A US6083524 A US 6083524A US 94473997 A US94473997 A US 94473997A US 6083524 A US6083524 A US 6083524A
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- United States
- Prior art keywords
- macromer
- biodegradable
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- poly
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- Expired - Lifetime
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- VPVXHAANQNHFSF-UHFFFAOYSA-N 1,4-dioxan-2-one Chemical compound O=C1COCCO1 VPVXHAANQNHFSF-UHFFFAOYSA-N 0.000 title claims abstract description 46
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 title claims abstract description 41
- 229920002988 biodegradable polymer Polymers 0.000 title 1
- 239000004621 biodegradable polymer Substances 0.000 title 1
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- -1 poly(ethylene glycol) Polymers 0.000 claims description 88
- 229920001223 polyethylene glycol Polymers 0.000 claims description 79
- YFHICDDUDORKJB-UHFFFAOYSA-N trimethylene carbonate Chemical compound O=C1OCCCO1 YFHICDDUDORKJB-UHFFFAOYSA-N 0.000 claims description 44
- 229920000642 polymer Polymers 0.000 claims description 33
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- VNQXSTWCDUXYEZ-UHFFFAOYSA-N 1,7,7-trimethylbicyclo[2.2.1]heptane-2,3-dione Chemical compound C1CC2(C)C(=O)C(=O)C1C2(C)C VNQXSTWCDUXYEZ-UHFFFAOYSA-N 0.000 claims description 3
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- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims 2
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 claims 1
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000000576 coating method Methods 0.000 description 15
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 15
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- 239000000203 mixture Substances 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 12
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- NIXOWILDQLNWCW-UHFFFAOYSA-M acrylate group Chemical group C(C=C)(=O)[O-] NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 9
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
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- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 7
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Classifications
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/64—Polyesters containing both carboxylic ester groups and carbonate groups
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0042—Materials resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/046—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0019—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
Definitions
- the present invention relates to improved photopolymerizable biodegradable hydrogels for use as tissue adhesives, coatings, sealants and in controlled drug delivery devices.
- the improved materials incorporate carbonate and/or dioxanone linkages. These biodegradable linkages allow improved control of various properties of the macromers, particularly increasing viscosity while preserving biodegradability.
- U.S. Pat. No. 5,410,016 to Hubbell et al. discloses biocompatible, biodegradable macromers which can be polymerized to form hydrogels.
- the macromers are block copolymers that include a biodegradable block, a water-soluble block with sufficient hydrophilic character to make the macromer water-soluble, and one or more polymerizable groups.
- the polymerizable groups are separated from each other by at least one degradable group, Hubbell specifically discloses using polyhydroxy acids, such as polylactide, polyglycolide and polycaprolactone as the biodegradable polymeric blocks.
- One of the disclosed uses for the macromers is to plug or seal leaks in tissue.
- hydrogels have been described, for example, in U.S. Pat. No. 4,938,763 to Dunn et al., U.S. Pat. Nos. 5,100,992 and 4,826,945 to Cohn et al., U.S. Pat. Nos. 4,741,872 and 5,160,745 to De Luca et al., U.S. Pat. No. 5,527,864 to Suggs et al., and U.S. Pat. No. 4,511,478 to Nowinski et al. Methods of using such polymers are described in U.S. Pat. No. 5,573,934 to Hubbell et al. and PCT WO 96/29370 by Focal.
- Sealing or plugging holes in lung tissue is inherently more difficult than sealing other types of tissue because the tissue is constantly expanded and contracted during normal respiration. It would be advantageous to provide macromers which can be rapidly polymerized in vivo to form hydrogels which are more elastic than conventional hydrogels, for example, for use in sealing lung tissue.
- Biocompatible, biodegradable, polymerizable and at least substantially water-soluble macromers and methods of preparation and use thereof are disclosed.
- the macromers are block copolymers that include at least one water-soluble block, at least one biodegradable block, and at least one polymerizable group.
- At least one of the biodegradable blocks comprises a linkage based on a carbonate or dioxanone group, and the macromers can contain other degradable linkages or groups in addition to carbonate or dioxanone.
- the carbonate and dioxanone linkages impart more elasticity to the polymer and degrade at a different rate than hydroxy acid linkages.
- Carbonate linkages can also increase macromer viscosity, at a given concentration, without requiring increased molecular weight of the nondegradable components of the macromer.
- the macromers can also include poly(hydroxy acid) linkages which degrade by hydrolysis into relatively non-toxic hydroxy acid residues, or other biodegradable blocks such as polycaprolactones, polyorthoesters, polyanhydrides, and polypeptides.
- the degradation time of the polymers can be controlled, for example, by selecting the types and proportion of the biodegradable blocks.
- the polymerizable groups can be polymerized by either free radical (homolytic) processes or by heterolytic processes (such as cationic polymerization). Preferably, the groups are polymerized photochemically.
- the macromer can be polymerized in the presence of prophylactic, therapeutic or diagnostic agents, for delivery of the incorporated agents in a controlled manner as the resulting polymer degrades.
- the macromers are useful for delivering hydrophobic, hydrophilic and/or labile materials. They can be particularly useful for delivery of hydrophobic materials.
- the macromers can be polymerized in an interfacial manner to form ultrathin coatings which are intimately adhered to the coated surface, or in a bulk manner to form relatively thick coatings which may or may not be intimately adhered to the coated surface.
- the two methods can be combined to provide a relatively thick coating which is intimately adhered to the surface. Each of these methods is advantageous for certain applications.
- FIG. 1 is a graph of the elastic strength (seal pressure, mm Hg) over time (hr) of five different sealant materials: 10% 35K T, 20% 35K T, 10% 20K TL, 10% 20 K TL, and 20% 35K TL K is defined as 100 Daltons (weight average molecular weight, T is trimethylene carbonate (TMC), L is lactide, and TL is a copolymer of TMC and lactide.
- TMC trimethylene carbonate
- L lactide
- TL is a copolymer of TMC and lactide.
- FIGS. 2A and 2B are graphs of the degradation (% mass loss) over time (days) for 20K T (FIG. 2A) and 35K T (FIG. 2B) for subcutaneous polymeric implants in rats.
- the macromers include at least one water-soluble block, at least one biodegradable block, and at least one polymerizable group. At least one biodegradable block contains a carbonate or dioxanone group. To obtain a biodegradable material after polymerization, each polymerizable group must be separated from any other polymerizable group on the macromer by at least one biodegradable linkage or group.
- At least a portion of the macromers will contain more than one reactive group and thereby be effective as crosslinkers, so that the macromers can be crosslinked to form a gel.
- the minimal proportion required will vary with the nature of the macromer and its concentration in solution, and the proportion of crosslinker in the macromer solution can be as high as 100% of the macromer solution.
- the macromers include at least 1.02 polymerizable groups on average, and, more preferably, the macromers each include two or more polymerizable groups on average.
- crosslinked hydrogels can be produced using only slightly more than one reactive group per macromer (i.e., about 1.02 polymerizable groups on average). However, higher percentages are preferable, and excellent gels can be obtained in polymer mixtures in which most or all of the molecules have two or more reactive double bonds.
- Poloxanines an example of a water-soluble block, have four arms and thus may readily be modified to include four polymerizable groups.
- a "biocompatible" material is one which stimulates only a mild, often transient, implantation response, as opposed to a severe or escalating response.
- a “biodegradable” material is one which decomposes under normal in vivo physiological conditions into components which can be metabolized or excreted.
- a "block” is a region of a copolymer differing in subunit composition from neighboring regions. Blocks will generally contain multiple subunits, up to about one thousand subunits or less for non-degradable materials, and without an upper limit for degradable materials. In the lower limit, the size of a block depends on its function; the minimum size is that which is sufficient to allow the function to be performed. In the case of a block conferring water-solubility on the macromer, this will be typically 400 daltons or more, preferably 600 daltons or more, more preferably at least 1000 daltons, and most preferably in the range of 2000 to 40,000 daltons.
- the minimum block size is a single linkage of the appropriate degradability for the function. More preferably, the block size is two to forty groups; most preferably, three to twenty.
- the reactive groups may be considered as a block for some purposes; the typical number of units in such a block is one, but may be two to five.
- a carbonate is a functional group with the structure --O--C(O)--O--.
- the carbonate starting material can be cyclic, such as trimethylene carbonate (TMC), or can be linear, such as dimethylcarbonate (CH 3 O--C(O)--OCH 3 ).
- TMC trimethylene carbonate
- CH 3 O--C(O)--OCH 3 dimethylcarbonate
- the carbonate will be present at least in part as R--O--C( ⁇ O)--O--R', where R and R' are other components of the macromer.
- a dioxanone is a repeating unit with the structure --O--C(O)--R--O--, where R is a straight, branched or cyclic alkyl group.
- R is a straight, branched or cyclic alkyl group.
- An example of a cyclic dioxanone is 1,4-dioxan-2-one. 1,4-dioxan-2-one is a preferred dioxanone.
- a hydrogel is a substance formed when an organic polymer (natural or synthetic) is cross-linked via covalent, ionic, or hydrogen bonds to create a three-dimensional open-lattice structure which entraps water molecules to form a gel.
- water-soluble is defined as a solubility of at least one gram/liter in an aqueous solution at a temperature in the range of about 0° C. and 50° C.
- Aqueous solutions can include small amounts of water-soluble organic solvents, such as dimethylsulfoxide, dimethylformamide, alcohols, acetone, and/or glymes.
- the macromers are block co-polymers that comprise a biodegradable block, a water-soluble block, and at least one polymerizable group.
- the macromers comprise at least 1.02 polymerizable groups on average, and, more preferably, include at least two polymerizable groups per macromer, on average. Average numbers of polymerizable groups can be obtained, for example, by blending macromers with different amounts of polymerizable groups.
- the individual polymeric blocks can be arranged to form different types of block copolymers, including di-block, tri-block, and multi-block copolymers.
- the polymerizable blocks can be attached directly to biodegradable blocks or indirectly via water-soluble nondegradable blocks, and are preferably attached so that the polymerizable groups are separated from each other by a biodegradable block.
- the macromer contains a water-soluble block coupled to a biodegradable block
- one polymerizable group may be attached to the water-soluble block and another attached to the biodegradable block.
- both polymerizable groups would be linked to the water-soluble block by at least one degradable linkage.
- the di-block copolymers include a water-soluble block linked to a biodegradable block, with one or both ends capped with a polymerizable group.
- the tri-block copolymers can include a central water-soluble block and outside biodegradable blocks, with one or both ends capped with a polymerizable group.
- the central block can be a biodegradable block
- the outer blocks can be water-soluble.
- the multiblock copolymers can include one or more of the water-soluble blocks and biocompatible blocks coupled together in a linear fashion.
- the multiblock copolymers can be brush, comb, dendritic or star copolymers.
- the backbone is formed of a water-soluble block
- at least one of the branches or grafts attached to the backbone is a biodegradable block.
- at least one of the branches or grafts attached to the backbone is a water-soluble block, unless the biodegradable block is also water-soluble.
- a multifunctional compound such as a polyol, can be coupled to multiple polymeric blocks, at least one of which is water-soluble and at least one of which is biodegradable.
- any formulation of the macromer which is intended to be biodegradable must be constructed so that each polymerizable group is separated from each other polymerizable group by one or more linkages which are biodegradable.
- Non-biodegradable materials are not subject to this constraint.
- the individual polymeric blocks may have uniform compositions, or may have a range of molecular weights, and may be combinations of relatively short chains or individual species which confer specifically desired properties on the final hydrogel, while retaining the required characteristics of the macromer.
- the lengths of oligomers referred to herein may vary from single units (in the biodegradable portions) to many, subject to the constraint of preserving the overall water-solubility of the macromer.
- xxK represents the molecular weight of the backbone polymer, which is polyethylene glycol ("PEG") unless otherwise stated, in thousands of Daltons.
- Z designates the biodegradable linkage, using a code wherein where L is for lactic acid, G is for glycolic acid, D is for dioxanone, C is for caprolactone, T is for trimethylene carbonate, and n is the average number of degradable groups in the block.
- the molecules are terminated with acrylic ester groups, unless otherwise stated. This is sometimes also indicated by the suffix A2.
- biodegradable groups in addition to carbonate or dioxanone
- natural materials may be used in the biodegradable sections when their degree of degradability is sufficient for the intended use of the macromer.
- biodegradable groups may comprise natural or unnatural amino acids, carbohydrate residues, and other natural linkages.
- Biodegradation time will be controlled by the local availability of enzymes hydrolyzing such linkages. The availability of such enzymes may be ascertained from the art or by routine experimentation.
- Suitable water-soluble polymeric blocks include those prepared from poly(ethylene glycol), poly(ethylene oxide), partially or fully hydrolyzed poly(vinyl alcohol), poly(vinylpyrrolidone), poly(ethyloxazoline), poly(ethylene oxide)-co-poly(propylene oxide) block copolymers (poloxamers and meroxapols), poloxamines, carboxymethyl cellulose, hydroxyalkylated celluloses such as hydroxyethyl cellulose and methylhydroxypropyl cellulose, polypeptides, polynucleotides, polysaccharides or carbohydrates such as Ficoll® polysucrose, hyaluronic acid, dextran, heparan sulfate, chondroitin sulfate, heparin, or alginate, and proteins such as gelatin, collagen, albumin, or ovalbumin.
- the water-soluble polymeric blocks are made from poly(ethylene glycol) or poly(ethylene oxide).
- the soluble polymer blocks may be intrinsically biodegradable or may be poorly biodegradable or effectively non-biodegradable in the body. In the latter two cases, the soluble blocks should be of sufficiently low molecular weight to allow excretion. The maximum molecular weight to allow excretion in human beings (or other species in which use is intended) will vary with polymer type, but will often be about 40,000 daltons or below. Water-soluble natural polymers and synthetic equivalents or derivatives, including polypeptides, polynucleotides, and degradable polysaccharides, can be used.
- the water-soluble blocks can be a single block with a molecular weight of at least 600, preferably 2000 or more, and more preferably at least 3000 Daltons.
- the water-soluble blocks can be two or more water-soluble blocks which are joined by other groups.
- Such joining groups can include biodegradable linkages, polymerizable linkages, or both.
- an unsaturated dicarboxylic acid such as maleic, fumaric, or aconitic acid
- two or more PEG molecules can be joined by biodegradable linkages including carbonate linkages, and subsequently be end-capped with polymerizable groups.
- the biodegradable blocks are preferably hydrolyzable under in vivo conditions. At least one biodegradable region is a carbonate or dioxanone linkage. Additional biodegradable polymeric blocks can include polymers and oligomers of hydroxy acids or other biologically degradable polymers that yield materials that are non-toxic or present as normal metabolites in the body.
- Preferred poly(hydroxy acid)s are poly(glycolic acid), poly(DL-lactic acid) and poly(L-lactic acid).
- Other useful materials include poly(amino acids), poly(anhydrides), poly(orthoesters), and poly(phosphoesters).
- Polylactones such as poly(epsilon-caprolactone), poly(delta-valerolactone), poly(gamma-butyrolactone)and poly (beta-hydroxybutyrate), for example, are also useful.
- Biodegradable regions can be constructed from monomers, oligomers or polymers using linkages susceptible to biodegradation, such as ester, peptide, anhydride, orthoester, and phosphoester bonds.
- the degradation time of hydrogels formed from the macromers can be controlled.
- Any carbonate can be used to make the macromers.
- Preferred carbonates are aliphatic carbonates, for maximum biocompatibility.
- trimethylene carbonate and dimethyl carbonate are examples of aliphatic carbonates.
- Lower dialkyl carbonates are joined to backbone polymers by removal by distillation of alcohols formed by equilibration of dialkyl carbonates with hydroxyl groups of the polymer.
- More preferred carbonates are the cyclic carbonates, which can react with hydroxy-terminated polymers without release of water.
- Suitable cyclic carbonates include ethylene carbonate (1,3-dioxolan-2-one), propylene carbonate (4-methyl -1,3-dioxolan-2-one), trimethylene carbonate (1,3-dioxan-2-one) and tetramethylene carbonate (1,3-dioxepan-2-one).
- orthocarbonates may react to give carbonates, or that carbonates may react with polyols via orthocarbonate intermediates, as described in Timberlake et al, U.S. Pat. No. 4,330,481.
- certain orthocarbonates, particularly dicyclic orthocarbonates can be suitable starting materials for forming the carbonate-linked macromers.
- suitable diols or polyols can be activated with phosgene to form chloroformates, as is described in the art, and these active compounds can be mixed with backbone polymers containing suitable groups, such as hydroxyl groups, to form macromers containing carbonate linkages.
- Suitable dioxanones include dioxanone (p-dioxanone; 1,4-dioxan-2-one; 2-keto-1,4-dioxane), and the closely related materials 1,4-dioxolan-2-one, 1,4-dioxepan-2-one and 1,5-dioxepan-2-one.
- Lower alkyl for example C1-C4 alkyl, derivatives of these compounds are also contemplated, such as 2-methyl p-dioxanone (cyclic O-hydroxyethyl ether of lactic acid).
- polymerizable group is defined as a reactive functional group that has the capacity to form additional covalent bonds resulting in macromer interlinking.
- Polymerizable groups specifically include groups capable of polymerizing via free radical polymerization and groups capable of polymerizing via cationic or heterolytic polymerization. Suitable groups include, but are not limited to, ethylenically or acetylenically unsaturated groups, isocyanates, epoxides (oxiranes), sulfhydryls, succinimides, maleimides, amines, imines, anides, carboxylic acids, sulfonic acids and phosphate groups.
- Ethylenically unsaturated groups include vinyl groups such as vinyl ethers, N-vinyl amides, allyl groups, unsaturated monocarboxylic acids, unsaturated dicarboxylic acids, and unsaturated tricarboxylic acids.
- Unsaturated monocarboxylic acids include acrylic acid, methacrylic acid and crotonic acid.
- Unsaturated dicarboxylic acids include maleic, fumaric, itaconic, mesaconic or citraconic acid.
- Unsaturated tricarboxylic acids include aconitic acid.
- Polymerizable groups may also be derivatives of such materials, such as acrylamide, N-isopropylacrylamide, hydroxyethylacrylate, hydroxyethylmethacrylate, and analogous vinyl and allyl compounds.
- Reactive group forming compounds will preferably be available in a stable activated form, to allow simple incorporation into the macromer. Examples of such materials are (meth)acrylyl chloride, acrylic anhydride, and allyl glycidyl ether.
- the polymerizable groups are preferably located at one or more ends of the macromer. In a less preferred embodiment, the polymerizable groups can be located within the macromer.
- Polymerization is initiated by any convenient reaction, including photopolymerization, chemical or thermal free-radical polymerization, redox reactions, cationic polymerization, and chemical reaction of active groups (such as isocyanates, for example.) Polymerization is preferably initiated using photoinitiators. Photoinitiators that generate a free radical or a cation on exposure to UV light are well known to those of skill in the art. Free-radicals can also be formed in a relatively mild manner from photon absorption of certain dyes and chemical compounds. The polymerizable groups are preferably polymerizable by free radical polymerization.
- the preferred polymerizable groups are acrylates, diacrylates, oligoacrylates, methacrylates, dimethacrylates, oligomethacrylates, cinnamates, dicinnamates, oligocinnamates, and other biologically acceptable photopolymerizable groups.
- These groups can be polymerized using photoinitiators that generate free radicals upon exposure to light, including UV (ultraviolet) and IR (infrared) light, preferably long-wavelength ultraviolet light (LWUV) or visible light. LWUV and visible light are preferred because they cause less damage to tissue and other biological materials than short-wave UV light.
- Useful photoinitiators are those which can be used to initiate polymerization of the macromers without cytotoxicity and within a short time frame, minutes at most and most preferably seconds.
- Light absorption by the dye causes the dye to assume a triplet state, and the triplet state subsequently reacts with the amine to form a free radical which initiates polymerization, either directly or via a suitable electron transfer reagent or co-catalyst, such as an amine.
- Polymerization can be initiated by irradiation with light at a wavelength of between about 200-1200 nm, most preferably in the long wavelength ultraviolet range or visible range, 320 nm or higher, and most preferably between about 365 and 550 nm.
- dyes can be used for photopolymerization. Suitable dyes are well known to those of skill in the art. Preferred dyes include erythrosin, phloxime, rose bengal, thionine, camphorquinone, ethyl eosin, eosin, methylene blue, riboflavin, 2,2-dimethyl-2-phenylacetophenone, 2-methoxy-2-phenylacetophenone, 2,2-dimethoxy-2-phenyl acetophenone, other acetophenone derivatives, and camphorquinone.
- Suitable cocatalysts include amines such as N-methyl diethanolamine, N,N-dimethyl benzylamine, triethanol amine, triethylamine, dibenzyl amine, N-benzylethanolamine, N-isopropyl benzylamine. Triethanolamine is a preferred cocatalyst.
- Suitable chemical, thermal and redox systems may initiate the polymerization of unsaturated groups by generation of free radicals in the initiator molecules, followed by transfer of these free radicals to the unsaturated groups to initiate a chain reaction.
- Peroxides and other peroxygen compounds are well-known in this regard, and may be considered as chemical or thermal initiators.
- Azobisbutyronitrile is a chemical initiator.
- a combination of a transition metal, especially iron, with a peroxygen and preferably a stabilizing agent such as glucuronic acid allows generation of free radicals to initiate polymerization by a cycling redox reaction.
- a macromer could be constructed with amine termination, with the amine considered as an active group; and another macromer could be constructed with isocyanate termination, with the isocyanate as the active group.
- an isocyanate-terminated macromer could be polymerized and crosslinked with a mixture of diamines and triamines. Such a reaction is more difficult to control than a photoinitiated reaction, but could be preferred for high volume extracorporeal production of gels for implantation, perhaps as drug delivery systems.
- Other pairs of reactants include maleimides with amines or sulfhydryls, or oxiranes with amines, sulfhydryls or hydroxyls.
- the macromers contain between about 0.3% and 20% by weight of carbonate residues or dioxanone residues, more preferably, between about 0.5% and 15% carbonate or dioxanone residues, and most preferably, about 1% to 5% carbonate or dioxanone residues.
- the macromer contains between about 0.1 and 10 residues per residue of carbonate or dioxanone, more preferably between about 0.2 and 5, and most preferably one or more such residue per macromer.
- the macromer includes a core, an extension on each end of the core, and an end cap on each extension.
- the core is a hydrophilic polymer or oligomer; each extension is a biodegradable oligomer comprising one or more carbonate or dioxanone linkage; and each end cap comprises one or more functional groups capable of cross-linking the macromers.
- the core includes hydrophilic poly(ethylene glycol) oligomers with a molecular weight between about 400 and 40,000 Da; each extension includes 1 to 10 residues selected from carbonate and dioxanone, and optionally further included between one and five hydroxyacid residues, preferably alpha-hydroxy acid residues; wherein the total of all residues in the extensions is sufficiently small to preserve water-solubility of the macromer, being typically less than about 20% of the weight of the macromer, more preferably 10% or less.
- each end cap includes a polymerizable group.
- the preferred groups are free-radical (homolytically) polymerizable. More preferably, they are ethylenically-unsaturated (i.e., containing carbon-carbon double bonds), with a preferred molecular weight between about 50 and 300 Da, which are capable of cross-linking and/or polymerizing the macromers.
- a preferred embodiment incorporates a core consisting of poly(ethylene glycol) oligomers of molecular weight about 25,000 Da; extensions including polycarbonate or poly(dioxanone) oligomers with a molecular weight of about 200 to 1000 D, alone or in combination with extensions formed of hydroxy acid oligomers; and end caps consisting of acrylate moieties (which are about 55 Da molecular weight).
- the macromers can be synthesized using means well known to those of skill in the art. General synthetic methods are found in the literature, for example in U.S. Pat. No. 5,410,016 to Hubbell et al., U.S. Pat. No. 4,243,775 to Rosensaft et al., and U.S. Pat. No. 4,526,938 to Churchill et al.
- a polyethylene glycol backbone can be reacted with trimethylene carbonate (TMC) or a similar carbonate in the presence of a Lewis acid catalyst, such as stannous octoate, to form a TMC-polyethylene glycol terpolymer.
- TMC-PEG polymer may optionally be further derivatized with additional degradable groups, such as lactate groups.
- additional degradable groups such as lactate groups.
- the terminal hydroxyl groups can then be reacted with acryloyl chloride in the presence of a tertiary amine to end-cap the polymer with acrylate end-groups.
- Similar coupling chemistry can be employed for macromers containing other water-soluble blocks, biodegradable blocks, and polymerizable groups, particularly those containing hydroxyl groups.
- the reaction can be either simultaneous or sequential. As shown in the examples below, the simultaneous reaction will produce an at least partially random copolymer of the three components. Sequential addition of a hydroxy acid after reaction of the PEG with the TMC will tend to produce an inner copolymer of TMC and one or more PEGs, which will statistically contain more than one PEG residue linked by linkages derived from TMC, with hydroxy acid largely at the ends of the (TMC, PEG) region. There is a tendency for TM and other carbonate groups to re-arrange by "back-biting" during synthesis, which is why multiple PEG molecules can become incorporated in the same macromer. When the hydroxy acid contains a secondary hydroxyl, as in lactic acid, then the tendency towards rearrangement is reduced.
- the degradable blocks or regions could be separately synthesized and then coupled to the backbone regions. In practice, this more complex reaction does not appear to be required to obtain useful materials.
- sequential addition of biodegradable groups to a carbonate-containing macromer can be used to enhance biodegradability of the macromer after capping with reactive end groups.
- TMC linkages in the resulting copolymers Upon reaction of, for example, trimethylene carbonate (TMC) with polyethylene glycol (PEG), the TMC linkages in the resulting copolymers have been shown to form end linked species of PEG, resulting in segmented copolymers, i.e. PEG units coupled by one or more adjacent TMC linkages.
- the length of the TMC segments can vary, and is believed to exhibit a statistical distribution. Coupling may also be accomplished via the carbonate subunit of TMC.
- segmented PEG/TMC copolymers form as a result of transesterification reactions involving the carbonate linkages of the TMC segments during the TMC polymerization process when a PEG diol is used as an initiator.
- the end-linking may begin during the reaction of the TMC with the PEG, and completion of the end linking and attainment of equilibrium is observable by a cessation of increase of the viscosity of the solution.
- a significant percentage of the macromer end groups can be PEG hydroxyls, resulting in the attachment of the reactive groups directly to one end of a non-biodegradable PEG molecule.
- a reaction of the PEG/TMC segmented copolymers can be prevented by adding additional segments of other hydrolyzable co-monomers (e.g. lactate, glycolate, 1,4-dioxanone, dioxepanone, caprolactone) on either end of the PEG/TMC segmented copolymer.
- Some scrambling of the comonomer segments with the PEG/TMC prepolymer is expected, but this can be minimized by using proper reaction conditions.
- the basic PEG/TMC segmented copolymer or the further reacted PEG/TMC/comonomer segmented terpolymer is then further reacted to form crosslinkable macromers by affixing reactive end groups (such as acrylates) to provide a macromer with reactive functionality. Subsequent reaction of the end groups in an aqueous environment results in a bioabsorbable hydrogel. Similar segmented structures would be expected if another polyalkylene glycol (PAG) were used, for example a poloxamer.
- PAG polyalkylene glycol
- the copolymers and macromers can have tailorable solubility and solution viscosity properties.
- the hydrogels can have tailorable modulus and degradation rate. For a given solution concentration in water, the viscosity is affected by the degree of end linking, the length of the TMC (and other hydrophobic species) segments, and the molecular weight of the starting PAG. The modulus of the hydrogel is affected by the molecular weight between crosslinks.
- the hydrogel degradation rate can be modified by adding a second, more easily hydrolyzed comonomer (e.g. lactate, glycolate, 1,4-dioxanone) as a segment on the ends of the basic PAG/TMC copolymer prior to adding the crosslinkable end group to form the macromer.
- a second, more easily hydrolyzed comonomer e.g. lactate, glycolate, 1,4-dioxanone
- a preferred application of the polymers is in a method of sealing leaks, for example, leaks of gases and/or bodily fluids (such as blood, cerebrospinal fluid, urine and bile), in tissue such as lung , urethra, ureter, gastrointestinal tract, reproductive tract, liver, spleen, dura, and the spinal cord.
- the method involves priming the surface of the tissue with a polymerization initiator, applying a macromer solution that also contains one or more polymerization initiators to the surface of the tissue to be coated, and then polymerizing the macromer.
- the polymerization initiator comprises a photoinitiator.
- an initiator in the macromer solution allows a relatively thick, for example 1 mm to 10 mm, layer of polymer to be formed on the tissue surface. Relatively thick polymer layers may be required to effectively seal some types of tissue, for example, lung tissue or dura, depending on the size of the leak.
- An advantage of the macromers when prepared with at least one carbonate group is that during the synthesis of the macromer, short blocks of non-biodegradable but excretable polymer, such as polyethylene oxide chains of up to about 40,000 D, can become linked by carbonate groups to give higher molecular weights to the macromers while preserving the biodegradability to secretable products of the macromer. It is believed that the higher molecular weights increase the elasticity of the final hydrogel. This is an important and useful property when the polymer must be readily and repeatedly stretched, as in a sealant layer applied to lung tissue. High elasticity can also be provided by linking nondegradable blocks with other polyfunctional linkers, such as dicarboxylic acids. However, since the synthetic chemistry required to make such macromers can be more complex than the simple reactions required for carbonate-based linking, this method is less preferred.
- Another preferred application is a method of reducing formation of adhesions after a surgical procedure in a patient.
- the method involves coating damaged tissue surfaces in a patient with an aqueous solution of a light-sensitive free-radical polymerization initiator and a macromer solution as described above.
- the coated tissue surfaces are exposed to light sufficient to polymerize the macromer.
- the light-sensitive free-radical polymerization initiator may be a single compound (e.g., 2,2-dimethoxy-2-phenyl acetophenone) or a combination of a dye and a cocatalyst (e.g., ethyl eosin or eosin Y, and triethanolamine).
- Another preferred application involves locally applying an incorporated agent, such as a prophylactic, therapeutic or diagnostic agent, to tissue surfaces of a patient.
- the method includes the steps of mixing an agent to be incorporated with an aqueous solution including a suitable polymerization initiator, such as a light-sensitive free-radical polymerization initiator, and a macromer, to form a coating mixture.
- a suitable polymerization initiator such as a light-sensitive free-radical polymerization initiator
- a macromer to form a coating mixture.
- Tissue surfaces are coated with the coating mixture and the macromer is polymerized, for example, by exposure of the coating mixture to an effective amount of light of an appropriate wavelength.
- any of a variety of therapeutic, prophylactic or diagnostic agents can be delivered using these methods.
- examples include synthetic and natural inorganic and organic compounds such as proteins (100 amino acid residues or more), peptides (less than 100 amino acid residues), carbohydrates, lipids, nucleic acid molecules, and small synthetic materials such as ethical drugs, having therapeutic, prophylactic or diagnostic activities.
- Nucleic acid molecules include genes, antisense molecules which bind to complementary DNA to inhibit transcription, aptamers, triple helix forming oligomers and ribozymes.
- the agents to be delivered can have a variety of biological activities. Diagnostic agents such as radiolabelled compounds, enzymatically labeled compounds, fluorescently labeled compounds, and other detectable agents can also be incorporated. Compounds with a wide range of molecular weights can be incorporated, for example, between 100 and 500,000 grams or more per mole.
- Therapeutic or prophylactic compounds of particular interest are those whose efficacy in treatment of a localized medical condition is increased by local delivery of the compound at or near the site of the localized medical condition.
- classes of such drugs are those which inhibit the formation or reformation of scars or adhesions; those which prevent unwanted proliferation of vascular tissue or other luminal tissue; and growth factors, cytokines, etc. which only needs to be effective locally.
- Imaging agents which may be utilized include commercially available agents used in positron emission tomography (PET), computer assisted tomography (CAT), single photon emission computerized tomography, x-ray, fluoroscopy, and magnetic resonance imaging (MRI).
- PET positron emission tomography
- CAT computer assisted tomography
- MRI magnetic resonance imaging
- Suitable materials for use as contrast agents in MRI include the gadolinium chelates currently available, such as diethylene triamine pentacetic acid (DTPA) and gadopentotate dimeglumine, as well as iron, magnesium, manganese, copper and chromium.
- DTPA diethylene triamine pentacetic acid
- gadopentotate dimeglumine as well as iron, magnesium, manganese, copper and chromium.
- Examples of materials useful for CAT and x-rays include iodine based materials for intravenous administration, such as ionic monomers typified by diatrizoate and iothalamate, non-ionic monomers such as iopamidol, isohexol, and ioversol, non-ionic dimers, such as iotrol and iodixanol, and ionic dimers, for example, ioxagalte.
- iodine based materials for intravenous administration such as ionic monomers typified by diatrizoate and iothalamate, non-ionic monomers such as iopamidol, isohexol, and ioversol, non-ionic dimers, such as iotrol and iodixanol, and ionic dimers, for example, ioxagalte.
- Hydrogels incorporating these agents can be detected using standard techniques available in the art and commercially available equipment.
- the macromers are particularly useful for delivering hydrophilic and/or labile materials. Because the macromer is water-soluble, water can penetrate the polymer and dissolve or extract incorporated hydrophilic materials. Labile materials can be incorporated without exposure of the material to organic solvents which would destroy biological activity. Hydrophobic materials may also be incorporated, if the rate of dissolution of the hydrophobic material and/or the gel matrix is sufficiently rapid to release the material at a therapeutically-effective rate. In all cases, the polymerized hydrogel will tend to protect the therapeutic material from attack by biological activities of the subject, such as enzyme activity.
- the macromers are polymerized with incorporated
- the macromers contain between about 0.3% and 20% by weight of carbonate residues or dioxanone residues, more preferably, between about 0.5% and 15% carbonate or dioxanone residues, and most preferably, about 1% to 5% carbonate or dioxanone residues.
- the macromer contains between about 0.1 and 10 residues per residue of carbonate or dioxanone, more preferably between about 0.2 and 5, and most preferably one or more such residue per macromer.
- the macromer includes a core, an extension on each end of the core, and an end cap on each extension.
- the core is a hydrophilic polymer or oligomer; each extension is a biodegradable oligomer comprising one or more carbonate or dioxanone linkage; and each end cap comprises one or more functional groups capable of cross-linking the macromers.
- the core includes hydrophilic poly(ethylene glycol) oligomers with a molecular weight between about 400 and 40,000 Da; each extension includes 1 to 10 residues selected from carbonate and dioxanone, and optionally further includes between one and five hydroxyacid residues, preferably alpha-hydroxy acid residues; wherein the total of all residues in the extensions is sufficiently small to preserve water-solubility of the macromer, being typically less than about 20% of the weight of the macromer, more preferably 10% or less.
- each end cap includes a polymerizable group.
- the preferred groups are free-radical (homolytically) polymerizable. More preferably, they are ethylenically-unsaturated (i.e., containing carbon-carbon double bonds), with a preferred molecular weight between about 50 and 300 Da, which are capable of cross-linking and/or polymerizing the macromers.
- a preferred embodiment incorporates a core consisting of poly(ethylene glycol) oligomers of molecular weight about 25,000 Da; extensions including polycarbonate or poly(dioxanone) oligomers with a molecular weight of about 200 to 1000 D, alone or in combination with extensions formed of hydroxy acid oligomers; and end caps consisting of acrylate moieties (which are about 55 Da molecular weight).
- the macromers, and hydrogels formed therefrom, can also be used to adhere tissue surfaces in a patient.
- the macromer is mixed with a suitable polymerization initiator system, such as a photoinitiator or photoinitiator/amine mixture, to form an aqueous mixture.
- a suitable polymerization initiator system such as a photoinitiator or photoinitiator/amine mixture
- the mixture is applied to a tissue surface to which tissue adhesion is desired.
- the tissue surface is contacted with the tissue with which adhesion is desired, forming a tissue junction.
- the macromers are then polymerized at the tissue junction.
- Such a technique can be used to hold surgically severed tissue in apposition during the healing process, thereby replacing or supplementing the use of sutures, staples, etc.
- a gel may also be used to form a protective barrier.
- an ultra thin coating is applied to the surface of a tissue, most preferably the inside surface of a blood vessel.
- Such coatings can be used to treat or prevent stenosis or restenosis of blood vessels.
- a polymerization initiator preferably a photoinitiator, is applied to the surface of the tissue, allowed to stain the tissue, and, optionally, the excess photoinitiator is removed by dilution or rinsing. After the initiator has been applied to the tissue, the macromer solution is applied and the macromer is polymerized.
- this method is capable of creating a uniform polymeric coating of between about one and 300 microns in thickness, more preferably about ten to 200 microns, most preferably 20 to 80 microns, which does not evoke thrombosis during its residence at the site.
- the surface of medical devices can be coated with the macromers using interfacial polymerization, bulk polymerization, or both, as discussed above. Coating layers applied using interfacial polymerization or a combination of interfacial and bulk polymerization typically adhere more strongly to the medical devices than those prepared using only bulk polymerization.
- Purified or as-supplied PEG was charged to a reactor, optionally with a small amount of xylene, and heated for five to six hours at about 110° C. (note: all temperatures herein are in degrees Celsius) under vacuum to complete removal of water. After cooling under vacuum, the flask was placed in a glove bag, the materials for forming the biodegradable linkages (including T (trimethylene carbonate) and L (lactide)) were added to the PEG, and the temperature was raised to about 160-165° C. under an argon blanket.
- T trimethylene carbonate
- L lactide
- a catalyst typically stannous octoate
- ring-opening addition was allowed to proceed for about 3 hours, with stirring under argon.
- the PEG-(T,L) intermediate could be further reacted at this stage, but typically was freed of unreacted monomers by precipitation in hexane, recovery and drying.
- the purified intermediate for example, PEG-(TnLm), where "n” is the number of T groups and “m” is the number of L groups, or the original reaction mixture without purification, was taken up in toluene, and an agent capable of adding unsaturated linkages, such as acryloyl chloride, was added, typically in excess, under mild heating (e.g., about 50° C.) and in the presence of an acid-neutralizing agent such as triethylamine. Suitable reactant ratios were found to be 1 ml acryloyl chloride and 1.8 ml triethylamine per 30 grams of PEG.
- the endcapped macromer, PEG-(T,L)-A2 was purified by precipitation in hexane, recovered and dried. Stabilizer was optionally added at this stage. The extent of incorporation of monomers was determined by NMR.
- the water would be removed azeotropically under mild reflux in, e.g., toluene; and the degradable linkages are preferably synthesized by polymerization onto the hydroxy compound as described above, although such blocks could be added as preformed activated acrylated blocks, for example, using a carbodiimide derivative of the acylated poly(degradable linkage), if greater control were required.
- 35K(T8)A2 (“35KT” in the examples below) was made from purified PEG of nominal molecular weight 35,000 by the melt procedure as described above. T was charged into the reactor at a nominal molar ratio of 13:1 to the PEG to obtain this result. The final actual acrylate incorporation averaged 1.6 per PEG molecule, or about 2 acrylates per macromer.
- 35K(T7L2)A2 contained about 7 T units (6.88 measured) and 2 lactate units (1.86 measured) as synthesized. (Note that there are 2 lactate units per lactide molecule.) T and L were charged at nominal molar ratios of 10:1 and 3:1 relative to PEG.
- 20K(T30L15)A2 contained about 30 T units and 15 lactide units per 20,000 D PEG molecule.
- the actual acrylate to PEG ratio was 1.42.
- Poly(ethylene glycol)-lactide-trimethylene carbonate terpolymers endcapped with acrylate esters were evaluated using a seal pressure test apparatus to determine the failure pressure for coatings prepared using the macromers.
- One of the materials tested had a poly(ethylene glycol) molecular weight of 20,000 Daltons (“20 kD”), a lactate incorporation of 13.8 and a trimethylene carbonate incorporation of 16.0, with nominal acrylation of 2 per macromer (“20KTL”). Also tested were 35 kD PEG esterified with about 8 TMC linkages and then endcapped with acrylates (“35KT”), and 35 kD PEG esterified with about 8 TMC and about 8 lactate groups (“35 KTL”), both also acrylated. The reagents applied were “primer” and "sealant”.
- the complete system contained both a photoinitiation system (Eosin Y/triethanolamine) and a redox initiation system (ferrous gluconate/fructose, plus t-butylhydroperoxide after mixing) which did not cause significant polymerization of the macromer until both mixed (primer and sealant) and activated by light.
- Primer solution contained Eosin Y (2000 ppm, w/w), 5000 ppm ferrous gluconate, 10,000 ppm (1%) fructose, 30,000 ppm NaCl, and 30% w/w of 3.5KL5 macromer (made according to U.S. Pat. No. 5,410,016). Primer was applied to a 2 cm ⁇ 2 cm piece of latex film (from a latex examination glove; about 1 mm thick) with a 6 mm diameter hole created in the center. A toroidal Teflon® fluoropolymer template with a 1 cm. diameter central hole was placed on the latex film to control the area of application of the sealant, by limiting its spread.
- Sealant solution contained macromer (in this example, 10% or 20% w/w of one of the macromers described above) dissolved in an aqueous solution containing isotonic saline, 90 mM triethanolamine as buffer and electron transfer component, Eosin Y (20 ppm) as a photoinitiator, 4000 ppm vinylcaprolactam as comonomer, and 125 ppm t-butylhydroperoxide as part of the light-sensitized redox initiation system. Two drops of sealant were dispensed inside the template above the hole and then carefully mixed in with the primer, using a brush.
- macromer in this example, 10% or 20% w/w of one of the macromers described above
- test apparatus was a modified membrane holder, in which the latex sample was clamped at the edges between gaskets. Pressure was then applied to the side of the latex away from the polymer seal, and the pressure required to rupture the seal was measured.
- FIG. 1 shows the results obtained with five different sealant materials.
- the seal pressure decreases over the course of time, presumably due to a combination of swelling of the hydrogel due to hydration and programmed degradation of the hydrogel.
- Poly(ethylene glycol)-trimethylene carbonate copolymers, optionally containing lactate, and endcapped with acrylate esters, were evaluated. Two of the materials described in Example 3 were used (20KTL and 35KT).
- the macromers were polymerized using visible light illumination from a xenon arc lamp (450-550 nm) at an intensity of 100 mW/cm 2 in a sealant solution containing macromer, eosin, triethanolamine, vinylcaprolactam, t-butylhydroperoxide and saline as in Example 3. Macromer concentration was 10% for 20KTL and 20% for 35KT.
- the absorption of the sealant was determined by subcutaneous implants in rats.
- Five female Sprague Dawley rats (250-300 g) were used in this study.
- the animals were anesthetized by intramuscular ("IM") injection of 3.2 ml/kg mixture of Ketamine (52.4 mg/kg), Xylazine (2.8 mg/kg), Acepromazine (0.7 mg/kg).
- IM intramuscular
- Four 1 cm longitudinal incisions were made through the skin on the back. Two incisions were made on each side of the spinal column, spaced 1 cm off the midline and 2 cm apart. A 2 ⁇ 2 cm pocket was created at each incision site by blunt dissection.
- Preformed hydrogel disks were prepared using sterile technique.
- sealant solution was placed in the bottom of one well of a standard 24-well tissue culture plate, and was illuminated for 40 sec at 100 mW/cm 2 , producing a thin disc about 18 mm. in diameter.
- One disk was placed in each subcutaneous pocket. Incisions were then closed with surgical staples. Animals were euthanized at intervals by CO 2 inhalation. Incisions were opened and gross observations were recorded. Each site was harvested and analyzed by gel permeation chromatography for mass loss.
- FIGS. 2A and 2B show that the 20KTL based hydrogels were completely absorbed in 20 days in vivo (FIG. 2A), whereas the 35KT based hydrogels were partially absorbed (60% weight loss) in 154 days (FIG. 2B). This illustrates the significant effect of rapidly-degrading linkages such as lactate groups.
- a poly(ethylene glycol)-trimethylene carbonate-lactate copolymer endcapped with acrylate ester (20KTL, from Example 2) was evaluated for its ability to seal fluid leaks in membranes in vivo.
- the poly(ethylene glycol) molecular weight used was 20,000 Da.
- the lactate incorporation was 13.8 and the trimethylene carbonate incorporation was 16.0.
- the macromer was fully acrylated.
- the performance of the sealant was evaluated in a dural incision injury model in three mongrel canines.
- the animals were pre-anesthetized, intubated and maintained on isoflurane gas anesthesia. With the head elevated, a bilateral craniotomy was created. Two dural incisions, each 2 cm. long, were made, one on the left side and one on the right side. Incisions were closed using 3 simple interrupted 4-0 to 6-0 silk sutures spaced approximately 5 mm apart. Cerebrospinal fluid (CSF) pressure was raised by inflating the lungs to 20 cm H 2 O, and the leak was assessed. All incisions were found to leak, as expected from the closure.
- CSF Cerebrospinal fluid
- the control side received no additional closure of the incision.
- the primer a low-viscosity solution; described in example 4
- the sealant (10% w/w solution of 20KTL (described above) with other materials as in Example 4) was layered over the primer, and the primer and sealant were mixed with a brush. Illumination for 40 sec. with a visible xenon arc lamp (450-550 nm) at an intensity of 100 mW/cm 2 was then performed to complete the polymerization.
- the leaks were re-verified by raising the CSF pressure by inflating the lungs to 20 cm H 2 O. Leakage was observed on the control side, but not on the experimental side. The bone flaps were replaced and the incision was repaired.
- the control sites showed a slight fibrosis present between the dura mater and calvarium. No inflammation was detected. The sealant was not apparent in two out of three animals and only small amounts were present in the third animal. The dural edges were approximated. Defects in the bone (resulting from the surgery) were filled with fibro-osseous tissue at 21 days, in both control and treated sites. Normal healing appeared to be taking place, both visually and histologically.
- Macromers can also be made by synthesis in solution. While requiring additional waste disposal, the solution synthesis is more easily controlled (compared to the melt synthesis of Example 1 or 2), and is preferred for most applications. This example also illustrates the practice of sequential addition of monomers; the method is also useful for simultaneous addition of monomers.
- 35KTLA was made by dissolving 75 g of 35kD (nominal) PEG in toluene to 20% w/w concentration, and was dried by nitrogen purge for 3 hours at 108° C. 3.06 G TMC (14 mole equivalents per PEG) and 0.024 g stannous octoate catalyst were added, and the solution was held at 108° for 4 hours with stirring. Then 0.46 g (1.5 equiv.) lactide was added, and stirring continued for 2 hrs. Then 300 ml toluene was added to give about a 10% wt/vol solution of polymer.
- 35KTLA2 was synthesized as described in Example 6.
- the completed macromer had a TMC:PEG molar ratio of 3.57; an acrylate: PEG ratio of 1.52; a lactate: PEG ratio of 1.39; and contained 766 ppm TMC.
- the macromer was 48.1% "monomer” (one PEG unit per macromer molecule), 46.3% “dimer” two PEG units per macromer molecule), 5.4% "trimer” and 0.1% higher oligomer.
- Discs of the macromer were made as described in example 4 and were incubated in phosphate-buffered saline, pH 7.4, at 37° and 57°. At 57°, half of the mass was lost at about 140 hrs, while at 37°, half the mass was lost at about 42 days. Mass loss was determined by rinsing the specimen, drying to constant weight, and correcting for the amount of buffer and salt present.
- Dioxanone (1,4-dioxan-2-one; p-dioxanone) was synthesized from DEG (diethylene glycol) essentially according to U.S. Pat. No. 2,807,629, Example 1. Two kilograms of DEG were mixed with 40 g. copper chromite (Aldrich) and heated at about 230° for 4 hours under nitrogen purge, which displaced generated hydrogen. Dioxanone and DEG were distilled from the mixture under vacuum at about 50° pot temperature. DEG was partially removed by extraction in cold (4°) diethyl ether. The partially purified material was dissolved in chloroform and applied to a silica column equilibrated in chloroform. Dioxanone was recovered in the initial fractions.
- DEG diethylene glycol
- Macromer 35KDA was made by drying overnight (vacuum, 110°) 15 g of 35K PEG, 1.7 g dioxanone, and 0.01 g of catalyst (stannous octoate). This is a ratio of 21:1 D:PEG. Samples were also made at other amounts of D (1.0 g, 18:1; 0.84 g, 15:1; 1.34 g, 24:1). Vials were sealed and heated at 150 for 5 hrs. Samples were dissolved in chloroform; optionally precipitated in ether; and acrylated as described in previous examples. NMR showed final molar ratios in the synthesized polymer of D/PEG, 1.82; Ac/PEG, 1.64.
- Macromer 35KDLA To a mixture of 15 g PEG, 0.84 g Dioxanone and 0.01 g catalyst was also added 0.39 g d,l-lactide. The mixture was dried, then incubated at 185° overnight; dissolved in chloroform and precipitated in ether, filtered and vacuum-dried; and acrylated with excess acryloyl chloride and triethylamine.
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Abstract
Description
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US09/479,520 US6177095B1 (en) | 1996-09-23 | 2000-01-07 | Polymerizable biodegradable polymers including carbonate or dioxanone linkages |
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US08/710,689 US5900245A (en) | 1996-03-22 | 1996-09-23 | Compliant tissue sealants |
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Cited By (114)
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---|---|---|---|---|
US6258382B1 (en) * | 1999-02-24 | 2001-07-10 | Takai Chemical Co. | Drug sustained-released biomaterial |
US20010056301A1 (en) * | 2000-03-13 | 2001-12-27 | Goupil Dennis W. | Hydrogel biomedical articles |
US6371975B2 (en) | 1998-11-06 | 2002-04-16 | Neomend, Inc. | Compositions, systems, and methods for creating in situ, chemically cross-linked, mechanical barriers |
US20020127196A1 (en) * | 2000-11-28 | 2002-09-12 | Focal, Inc. | Polyalkylene glycol viscosity-enhancing polymeric formulations |
US6458147B1 (en) | 1998-11-06 | 2002-10-01 | Neomend, Inc. | Compositions, systems, and methods for arresting or controlling bleeding or fluid leakage in body tissue |
US20020173586A1 (en) * | 2000-09-28 | 2002-11-21 | Jeong Byeong Moon | Thermogelling biodegradable aqueous polymer solution |
US20020187182A1 (en) * | 2001-02-14 | 2002-12-12 | Genzyme Corporation | Biocompatible fleece for hemostasis and tissue engineering |
US20030100921A1 (en) * | 1998-11-06 | 2003-05-29 | Neomend, Inc. | Systems, methods, and compositions for achieving closure of vascular puncture sites |
US6572839B2 (en) * | 2000-03-09 | 2003-06-03 | Hitachi, Ltd. | Sensitizer for tumor treatment |
US20030104347A1 (en) * | 2000-03-21 | 2003-06-05 | Yuichi Mori | Coating material for living organism tissue, coated product from living organism tissue and method of coating living organism material |
WO2003047462A1 (en) * | 2001-03-12 | 2003-06-12 | Clemson University | Polysaccharide-based polmerizable hydrogels |
US20030211073A1 (en) * | 2000-03-13 | 2003-11-13 | Goupil Dennis W. | Tissue bulking and coating compositions |
US6673385B1 (en) * | 2000-05-31 | 2004-01-06 | Advanced Cardiovascular Systems, Inc. | Methods for polymeric coatings stents |
US6676971B2 (en) | 2000-03-13 | 2004-01-13 | Biocure, Inc. | Embolic compositions |
US6713593B2 (en) * | 2000-10-11 | 2004-03-30 | Pohang Iron & Steel Co., Ltd. | Copolymer comprising alkylene carbonate and method of preparing same |
US20040077780A1 (en) * | 2000-09-28 | 2004-04-22 | Battelle Memorial Institute | Thermogelling oligopeptide polymers |
US20040091462A1 (en) * | 2002-08-20 | 2004-05-13 | Lin Steve T. | Composition for the carrying and delivery of bone growth inducing material and methods for producing and applying the composition |
US6743248B2 (en) | 1996-12-18 | 2004-06-01 | Neomend, Inc. | Pretreatment method for enhancing tissue adhesion |
KR100451910B1 (en) * | 2000-10-05 | 2004-10-08 | 주식회사 바이오폴리테크 | A water soluble and biodegradable polymer gel, and a process of preparing for the same |
US20040228902A1 (en) * | 2003-05-13 | 2004-11-18 | Medtronic, Inc. | Moisture curable materials for delivery of agents, methods, and medical devices |
US20040228794A1 (en) * | 1998-04-10 | 2004-11-18 | Battelle Memorial Institute | Therapeutic agent carrier compositions |
US6830756B2 (en) | 1998-11-06 | 2004-12-14 | Neomend, Inc. | Systems, methods, and compositions for achieving closure of vascular puncture sites |
US20050002893A1 (en) * | 2001-10-24 | 2005-01-06 | Helmut Goldmann | Composition consisting of a polymer containing amino groups and an aldehyde containing at least three aldehyde groups |
US20050004324A1 (en) * | 2003-05-21 | 2005-01-06 | Ward Robert S. | Permselective structurally robust membrane material |
WO2005002596A1 (en) * | 2003-07-03 | 2005-01-13 | Universiteit Twente | Biocompatible polymer networks |
US6899889B1 (en) | 1998-11-06 | 2005-05-31 | Neomend, Inc. | Biocompatible material composition adaptable to diverse therapeutic indications |
US20050178395A1 (en) * | 2003-11-20 | 2005-08-18 | Angiotech International Ag | Polymer compositions and methods for their use |
US6949114B2 (en) | 1998-11-06 | 2005-09-27 | Neomend, Inc. | Systems, methods, and compositions for achieving closure of vascular puncture sites |
US20050234121A1 (en) * | 2004-03-24 | 2005-10-20 | Binder Thomas P | Vegetable based dioxanone derivatives, synthesis and uses thereof |
US20050244455A1 (en) * | 2004-04-20 | 2005-11-03 | Greenawalt Keith E | Surgical prosthesis |
US20050271727A1 (en) * | 2004-06-07 | 2005-12-08 | Callisyn Pharmaceuticals, Inc. | Biodegradable and biocompatible crosslinked polymer hydrogel prepared from PVA and/or PEG macromer mixtures |
US20050281866A1 (en) * | 2004-05-24 | 2005-12-22 | Genzyme Corporation | Adherent polymeric compositions |
US6979464B2 (en) | 1997-06-06 | 2005-12-27 | Battelle Memorial Institute | Reversible geling co-polymer and method of making |
US20050287218A1 (en) * | 2004-06-29 | 2005-12-29 | Hassan Chaouk | Biomaterial |
US6994686B2 (en) | 1998-08-26 | 2006-02-07 | Neomend, Inc. | Systems for applying cross-linked mechanical barriers |
WO2006014067A1 (en) | 2004-08-02 | 2006-02-09 | Samyang Corporation | Biodegradable multi-block polymeric composition capable of sol-gel transition |
US7022343B2 (en) | 2000-12-27 | 2006-04-04 | Genzyme Corporation | Controlled release of anti-arrhythmic agents |
US20060183871A1 (en) * | 2003-05-21 | 2006-08-17 | Ward Robert S | Biosensor membrane material |
US20060239961A1 (en) * | 2002-02-15 | 2006-10-26 | Nektar Therapeutics Al, Corporation | Hydrolytically degradable alkylene oxide based polymers |
US20070065481A1 (en) * | 2005-09-21 | 2007-03-22 | Chudzik Stephen J | Coatings including natural biodegradable polysaccharides and uses thereof |
US20070112115A1 (en) * | 2005-11-15 | 2007-05-17 | Shalaby Shalaby W | Inorganic-organic hybrid micro-/nanofibers |
US20070149641A1 (en) * | 2005-12-28 | 2007-06-28 | Goupil Dennis W | Injectable bone cement |
US20070155926A1 (en) * | 2003-03-28 | 2007-07-05 | Krzysztof Matyjaszewski | Degradable polymers |
US20070237803A1 (en) * | 2006-04-11 | 2007-10-11 | Medtronic Vascular, Inc. | Biodegradable Biocompatible Amphiphilic Copolymers for Coating and Manufacturing Medical Devices |
US20070276101A1 (en) * | 2004-03-05 | 2007-11-29 | Carnegie Mellon Uiniversity | Atom Transfer Radical Polymerization Process |
US20080077179A1 (en) * | 1997-03-12 | 2008-03-27 | Neomend, Inc. | Pretreatment method for enhancing tissue adhesion |
EP1904553A1 (en) * | 2005-07-06 | 2008-04-02 | Molly S. Shoichet | Method of biomolecule immobilization on polymers using click-type chemistry |
US20080140114A1 (en) * | 1997-03-12 | 2008-06-12 | Neomend, Inc. | Systems and methods for sealing a vascular puncture |
US20080161848A1 (en) * | 2002-05-03 | 2008-07-03 | Biopsy Sciences, Llc | Biodegradable polymer for making tissue and sealing tracts |
US20090030451A1 (en) * | 2005-02-09 | 2009-01-29 | Hadba Ahmad R | Synthetic Sealants |
US20090117188A1 (en) * | 2007-11-02 | 2009-05-07 | Gershkovich Julia B | Methods of Augmenting or Repairing Soft Tissue |
CN100497437C (en) * | 2003-11-17 | 2009-06-10 | 中国科学院过程工程研究所 | Preparation method of polyethylene carboxylic acid and its use |
KR100927533B1 (en) * | 2007-10-23 | 2009-11-17 | 한남대학교 산학협력단 | Polyhydroxyethyl aspartamide-polyparadioxanone copolymer and preparation method thereof |
US20090294049A1 (en) * | 2008-06-02 | 2009-12-03 | Medtronic Vascular, Inc. | Biodegradable Adhesive Hydrogels |
US20090312505A1 (en) * | 2005-08-26 | 2009-12-17 | Krzysztof Matyjaszewski | Polymerization Process with catalyst reactivation |
US7682648B1 (en) | 2000-05-31 | 2010-03-23 | Advanced Cardiovascular Systems, Inc. | Methods for forming polymeric coatings on stents |
US7700819B2 (en) | 2001-02-16 | 2010-04-20 | Kci Licensing, Inc. | Biocompatible wound dressing |
US20100143286A1 (en) * | 2006-10-09 | 2010-06-10 | Carnegie Mellon University | Preparation of functional gel particles with a dual crosslink network |
US7763769B2 (en) | 2001-02-16 | 2010-07-27 | Kci Licensing, Inc. | Biocompatible wound dressing |
US20100249271A1 (en) * | 2007-05-23 | 2010-09-30 | Carnegie Mellon University | Hybrid partice composite structures with reduced scattering |
US20110086014A1 (en) * | 2008-06-18 | 2011-04-14 | Ishay Attar | Method for enzymatic cross-linking of a protein |
US20110112573A1 (en) * | 2008-06-18 | 2011-05-12 | Orahn Preiss Bloom | Methods and devices for use with sealants |
US20110110882A1 (en) * | 2008-06-18 | 2011-05-12 | Orahn Preiss-Bloom | Cross-linked compositions |
US20110142936A1 (en) * | 2009-12-15 | 2011-06-16 | Patrick Campbell | Implants and biodegradable fiducial markers |
US8133484B2 (en) | 2006-12-15 | 2012-03-13 | Lifebond Ltd | Hemostatic materials and dressing |
US20120143300A1 (en) * | 2009-05-20 | 2012-06-07 | Arsenal Medical | Medical implant |
US8252880B2 (en) | 2007-05-23 | 2012-08-28 | Carnegie Mellon University | Atom transfer dispersion polymerization |
US8273823B2 (en) | 2005-08-23 | 2012-09-25 | Carnegie Mellon University | Atom transfer radical polymerization in microemulsion and true emulsion polymerization processes |
US20120308481A1 (en) * | 2003-08-11 | 2012-12-06 | Pathak Holdings Llc | Radio-opaque compounds, compositions containing same and methods of their synthesis and use |
US8409606B2 (en) | 2009-02-12 | 2013-04-02 | Incept, Llc | Drug delivery through hydrogel plugs |
US20130304177A1 (en) * | 2009-05-20 | 2013-11-14 | Maria Palasis | Drug Eluting Medical Implant |
US20130317600A1 (en) * | 2009-05-20 | 2013-11-28 | Maria Palasis | Drug eluting medical implant |
US8722039B2 (en) | 2006-12-15 | 2014-05-13 | Lifebond Ltd. | Gelatin-transglutaminase hemostatic dressings and sealants |
US20140148558A1 (en) * | 2010-09-21 | 2014-05-29 | Centre National De La Recherche Scientifique(Cnrs) | One-step, one-pot process for preparing multiblock and gradient copolymer |
US8961544B2 (en) | 2010-08-05 | 2015-02-24 | Lifebond Ltd. | Dry composition wound dressings and adhesives comprising gelatin and transglutaminase in a cross-linked matrix |
US8962764B2 (en) | 2009-03-27 | 2015-02-24 | Carnegie Mellon University | Preparation of functional star macromolecules |
US8961501B2 (en) | 2010-09-17 | 2015-02-24 | Incept, Llc | Method for applying flowable hydrogels to a cornea |
US8992601B2 (en) | 2009-05-20 | 2015-03-31 | 480 Biomedical, Inc. | Medical implants |
US9066991B2 (en) | 2009-12-22 | 2015-06-30 | Lifebond Ltd. | Modification of enzymatic crosslinkers for controlling properties of crosslinked matrices |
US9125807B2 (en) | 2007-07-09 | 2015-09-08 | Incept Llc | Adhesive hydrogels for ophthalmic drug delivery |
US9205150B2 (en) | 2011-12-05 | 2015-12-08 | Incept, Llc | Medical organogel processes and compositions |
US9232805B2 (en) | 2010-06-29 | 2016-01-12 | Biocure, Inc. | In-situ forming hydrogel wound dressings containing antimicrobial agents |
US9309347B2 (en) | 2009-05-20 | 2016-04-12 | Biomedical, Inc. | Bioresorbable thermoset polyester/urethane elastomers |
US9533297B2 (en) | 2012-02-23 | 2017-01-03 | Carnegie Mellon University | Ligands designed to provide highly active catalyst complexes |
US9644042B2 (en) | 2010-12-17 | 2017-05-09 | Carnegie Mellon University | Electrochemically mediated atom transfer radical polymerization |
US9737647B2 (en) | 2009-05-20 | 2017-08-22 | Arsenal Medical, Inc. | Drug-eluting medical implants |
US20170274102A1 (en) * | 2014-08-15 | 2017-09-28 | The Johns Hopkins University | Post-surgical imaging marker |
US9982070B2 (en) | 2015-01-12 | 2018-05-29 | Carnegie Mellon University | Aqueous ATRP in the presence of an activator regenerator |
US10072042B2 (en) | 2011-08-22 | 2018-09-11 | Carnegie Mellon University | Atom transfer radical polymerization under biologically compatible conditions |
US10226417B2 (en) | 2011-09-16 | 2019-03-12 | Peter Jarrett | Drug delivery systems and applications |
WO2019067441A1 (en) | 2017-09-26 | 2019-04-04 | Devicor Medical Products, Inc. | Biopsy site marker with microsphere coating |
US10335124B1 (en) | 2016-02-29 | 2019-07-02 | Devicor Medical Products, Inc. | Marker delivery device with adaptor for biopsy site marking and method of use thereof |
US10610841B1 (en) | 2016-06-30 | 2020-04-07 | Devicor Medical Products, Inc. | Marker having enhanced ultrasound visibility and method of manufacturing the same |
US10617563B2 (en) | 2015-07-22 | 2020-04-14 | Incept, Llc | Coated implants |
WO2020123350A1 (en) | 2018-12-10 | 2020-06-18 | Devicor Medical Products, Inc. | Biopsy system with end deploy needle |
WO2020131654A1 (en) | 2018-12-17 | 2020-06-25 | Devicor Medical Products, Inc. | Apparatus for delivering biopsy cavity marker |
WO2020168026A1 (en) | 2019-02-15 | 2020-08-20 | Devicor Medical Products, Inc. | Marker delivery device with sterile guide |
WO2020243386A1 (en) | 2019-05-30 | 2020-12-03 | Devicor Medical Products, Inc. | Shape memory marker deployment device |
WO2020243474A1 (en) | 2019-05-30 | 2020-12-03 | Devicor Medical Products, Inc. | Biopsy site marker for limited migration |
WO2020243470A1 (en) | 2019-05-30 | 2020-12-03 | Devicor Medical Products, Inc. | Methods and apparatus for direct marking |
WO2021146367A2 (en) | 2020-01-15 | 2021-07-22 | Devicor Medical Products, Inc. | Marker delivery device with push rod having actuation features |
US11090132B2 (en) | 2017-09-15 | 2021-08-17 | Devicor Medical Products, Inc. | Method for manufacturing marker with aerated hydrogel |
WO2021188479A1 (en) | 2020-03-17 | 2021-09-23 | Devicor Medical Products, Inc. | Non-migrating biopsy site identifiers |
US11174325B2 (en) | 2017-01-12 | 2021-11-16 | Carnegie Mellon University | Surfactant assisted formation of a catalyst complex for emulsion atom transfer radical polymerization processes |
EP3781384A4 (en) * | 2018-04-19 | 2022-01-26 | Poly-Med Inc. | Macromers and compositions for photocuring processes |
WO2022119911A1 (en) | 2020-12-02 | 2022-06-09 | Devicor Medical Products, Inc. | A marker delivery device configured to decouple plunger and push rod |
US11447602B2 (en) | 2018-09-26 | 2022-09-20 | Sofradim Production | Biodegradable triblock copolymers and implantable medical devices made therefrom |
WO2023215090A1 (en) | 2022-05-03 | 2023-11-09 | Devicor Medical Products, Inc. | Biopsy site marker with increased visualization and non-migration features |
WO2023249760A1 (en) | 2022-06-23 | 2023-12-28 | Devicor Medical Products, Inc. | Biopsy site marker with expandable mesh |
WO2024039561A1 (en) | 2022-08-16 | 2024-02-22 | Devicor Medical Products, Inc. | Biopsy site marker having movable portions |
WO2024039560A1 (en) | 2022-08-16 | 2024-02-22 | Devicor Medical Products, Inc. | Biopsy site marker having expandable portion |
WO2024086055A1 (en) | 2022-10-21 | 2024-04-25 | Devicor Medical Products, Inc. | Biopsy device with end deployment for marker delivery |
DE102023128960A1 (en) | 2022-10-21 | 2024-05-02 | Devicor Medical Products, Inc. | FLUID DEPLOYMENT MECHANISM FOR BIOPSY SITE MARKER |
US11998654B2 (en) | 2018-07-12 | 2024-06-04 | Bard Shannon Limited | Securing implants and medical devices |
Families Citing this family (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8003705B2 (en) | 1996-09-23 | 2011-08-23 | Incept Llc | Biocompatible hydrogels made with small molecule precursors |
WO1999034833A1 (en) * | 1998-01-07 | 1999-07-15 | Shearwater Polymers, Incorporated | Degradable heterobifunctional poly(ethylene glycol) acrylates and gels and conjugates derived therefrom |
US6165193A (en) * | 1998-07-06 | 2000-12-26 | Microvention, Inc. | Vascular embolization with an expansible implant |
US7351249B2 (en) * | 1998-11-06 | 2008-04-01 | Neomend, Inc. | Systems, methods, and compositions for achieving closure of suture sites |
JP2002531217A (en) | 1998-12-04 | 2002-09-24 | チャンドラシェカー ピー. パサック, | Biocompatible crosslinked polymer |
US6423818B1 (en) * | 1999-07-30 | 2002-07-23 | Takehisa Matsuda | Coumarin endcapped absorbable polymers |
EP1142596A1 (en) * | 2000-04-03 | 2001-10-10 | Universiteit Gent | Compositions of crosslinkable prepolymers for use in therapeutically active biodegradable implants |
EP1992317B1 (en) * | 2000-08-30 | 2012-02-29 | Johns Hopkins University | Devices for intraocular drug delivery |
US6794485B2 (en) * | 2000-10-27 | 2004-09-21 | Poly-Med, Inc. | Amorphous polymeric polyaxial initiators and compliant crystalline copolymers therefrom |
US6994722B2 (en) | 2001-07-03 | 2006-02-07 | Scimed Life Systems, Inc. | Implant having improved fixation to a body lumen and method for implanting the same |
US7572288B2 (en) | 2001-07-20 | 2009-08-11 | Microvention, Inc. | Aneurysm treatment device and method of use |
US8252040B2 (en) | 2001-07-20 | 2012-08-28 | Microvention, Inc. | Aneurysm treatment device and method of use |
US8715312B2 (en) * | 2001-07-20 | 2014-05-06 | Microvention, Inc. | Aneurysm treatment device and method of use |
US6790455B2 (en) * | 2001-09-14 | 2004-09-14 | The Research Foundation At State University Of New York | Cell delivery system comprising a fibrous matrix and cells |
US6932833B1 (en) | 2002-04-01 | 2005-08-23 | Bobby W. Presley | Method and barrier for limiting fluid movement through a tissue rent |
US7148315B2 (en) * | 2002-10-23 | 2006-12-12 | Ethicon, Inc. | Monomer addition techniques to control manufacturing of bioabsorbable copolymers |
US20040151691A1 (en) * | 2003-01-30 | 2004-08-05 | Oxman Joel D. | Hardenable thermally responsive compositions |
US20040185013A1 (en) * | 2003-01-30 | 2004-09-23 | Burgio Paul A. | Dental whitening compositions and methods |
US7223826B2 (en) * | 2003-01-30 | 2007-05-29 | 3M Innovative Properties Company | Amide-functional polymers, compositions, and methods |
US8021680B2 (en) * | 2003-05-02 | 2011-09-20 | Surmodics, Inc. | Controlled release bioactive agent delivery device |
US8246974B2 (en) * | 2003-05-02 | 2012-08-21 | Surmodics, Inc. | Medical devices and methods for producing the same |
US8348971B2 (en) * | 2004-08-27 | 2013-01-08 | Accessclosure, Inc. | Apparatus and methods for facilitating hemostasis within a vascular puncture |
ITTO20040918A1 (en) * | 2004-12-29 | 2005-03-29 | Luigi Ambrosio | POLYMERIC HYDROGEL BIODEGRADABLE ABSORBERS AND PROCEDURE FOR THEIR PREPARATION |
US20060149363A1 (en) * | 2005-01-06 | 2006-07-06 | Scimed Life Systems, Inc. | Optimally expanded, collagen sealed ePTFE graft with improved tissue ingrowth |
US8133553B2 (en) | 2007-06-18 | 2012-03-13 | Zimmer, Inc. | Process for forming a ceramic layer |
US8309521B2 (en) | 2007-06-19 | 2012-11-13 | Zimmer, Inc. | Spacer with a coating thereon for use with an implant device |
CN101842061A (en) * | 2007-06-25 | 2010-09-22 | 微排放器公司 | Self-expanding prosthesis |
US8062655B2 (en) * | 2007-08-31 | 2011-11-22 | Phillips Plastics Corporation | Composite scaffold structure |
US8608049B2 (en) * | 2007-10-10 | 2013-12-17 | Zimmer, Inc. | Method for bonding a tantalum structure to a cobalt-alloy substrate |
US20110230973A1 (en) * | 2007-10-10 | 2011-09-22 | Zimmer, Inc. | Method for bonding a tantalum structure to a cobalt-alloy substrate |
US20090187256A1 (en) * | 2008-01-21 | 2009-07-23 | Zimmer, Inc. | Method for forming an integral porous region in a cast implant |
US20090198286A1 (en) * | 2008-02-05 | 2009-08-06 | Zimmer, Inc. | Bone fracture fixation system |
US8745133B2 (en) * | 2008-03-28 | 2014-06-03 | Yahoo! Inc. | System and method for optimizing the storage of data |
US20110190323A1 (en) * | 2008-08-28 | 2011-08-04 | President And Fellows Of Harvard College | Cortistatin analogues and syntheses thereof |
CN101864069B (en) * | 2010-06-10 | 2012-02-22 | 武汉大学 | Biodegradable hydrogel and synthesis method thereof |
EP2707077B1 (en) | 2011-05-11 | 2017-10-04 | Microvention, Inc. | Device for occluding a lumen |
US9827401B2 (en) | 2012-06-01 | 2017-11-28 | Surmodics, Inc. | Apparatus and methods for coating medical devices |
US9308355B2 (en) | 2012-06-01 | 2016-04-12 | Surmodies, Inc. | Apparatus and methods for coating medical devices |
EP3505521A1 (en) | 2013-12-24 | 2019-07-03 | President and Fellows of Harvard College | Cortistatin analogues and syntheses and uses thereof |
CN104119486B (en) * | 2014-06-27 | 2017-02-08 | 重庆阮氏塑业有限公司 | Polycarbonate composite material and preparation method thereof |
EP3294298A4 (en) | 2015-05-08 | 2018-10-17 | President and Fellows of Harvard College | Cortistatin analogues, syntheses, and uses thereof |
EP3316889A4 (en) | 2015-07-01 | 2018-11-14 | President and Fellows of Harvard College | Cortistatin analogues and syntheses and uses thereof |
US11628466B2 (en) | 2018-11-29 | 2023-04-18 | Surmodics, Inc. | Apparatus and methods for coating medical devices |
EP3680273B1 (en) * | 2019-01-08 | 2022-03-09 | Université de Montpellier | Branched-block copolymer photo-crosslinker functionalized with photoreactive groups and its use for shaping degradable photo-crosslinked elastomers suitable for medical and tissue-engineering applications |
US11819590B2 (en) | 2019-05-13 | 2023-11-21 | Surmodics, Inc. | Apparatus and methods for coating medical devices |
US20220323637A1 (en) * | 2019-06-26 | 2022-10-13 | Davol Inc. | Reactive dry powdered hemostatic materials comprising a nucleophile and a multifunctional modified polyethylene glycol based crosslinking agent |
US11739166B2 (en) | 2020-07-02 | 2023-08-29 | Davol Inc. | Reactive polysaccharide-based hemostatic agent |
Citations (218)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2155658A (en) * | 1936-01-08 | 1939-04-25 | Chemische Forschungs Gmbh | Surgical and medical preparations |
US2210817A (en) * | 1939-04-19 | 1940-08-06 | Du Pont | Superpolycarbonate |
US2517985A (en) * | 1948-06-22 | 1950-08-08 | Malcom A Davis | Chimney for liquid fuel burners |
US2668162A (en) * | 1952-03-20 | 1954-02-02 | Du Pont | Preparation of high molecular weight polyhydroxyacetic ester |
US2683136A (en) * | 1950-10-25 | 1954-07-06 | Du Pont | Copolymers of hydroxyacetic acid with other alcohol acids |
US2703316A (en) * | 1951-06-05 | 1955-03-01 | Du Pont | Polymers of high melting lactide |
US2789968A (en) * | 1953-12-08 | 1957-04-23 | Eastman Kodak Co | Polycarbonates from polymethylene glycol-bis |
US2917410A (en) * | 1955-06-20 | 1959-12-15 | American Cyanamid Co | Polyglycol-polyacid ester treatment of textiles |
US2962524A (en) * | 1957-04-18 | 1960-11-29 | Chich | |
US3021310A (en) * | 1959-12-03 | 1962-02-13 | Union Garbide Corp | Polymerization of cyclic esters |
US3030331A (en) * | 1957-08-22 | 1962-04-17 | Gen Electric | Process for preparing copolyesters comprising reacting a carbonyl halide with a dicarboxylic acid and a dihydroxy compound in the presence of a tertiary amine |
US3046255A (en) * | 1957-06-20 | 1962-07-24 | Pittsburgh Plate Glass Co | Process for preparing polycarbonates |
US3063968A (en) * | 1960-06-15 | 1962-11-13 | Gen Aniline & Film Corp | Polymerization of 2-p-dioxanone |
GB965085A (en) | 1959-07-17 | 1964-07-29 | Eastman Kodak Co | Block copolycarbonates |
US3157622A (en) * | 1961-01-03 | 1964-11-17 | Gen Electric | Resinous compositions |
US3161615A (en) * | 1957-02-05 | 1964-12-15 | Gen Electric | Resinous copolymeric polycarbonate of a mixture of dihydric phenols |
US3169121A (en) * | 1957-08-22 | 1965-02-09 | Gen Electric | Carbonate-carboxylate copolyesters of dihydric phenols and difunctional carboxylic acids |
US3223083A (en) * | 1960-09-09 | 1965-12-14 | President And Directors Of Geo | Method for adhesively securing together skin and other soft tissue and bone |
US3268486A (en) * | 1963-06-28 | 1966-08-23 | Shell Oil Co | Process for preparing polyesters |
US3268487A (en) * | 1963-12-23 | 1966-08-23 | Shell Oil Co | Process for polymerization of lactides |
US3297033A (en) * | 1963-10-31 | 1967-01-10 | American Cyanamid Co | Surgical sutures |
US3301824A (en) * | 1963-09-26 | 1967-01-31 | Union Carbide Corp | Polymers of cyclic carbonates |
US3301825A (en) * | 1963-09-26 | 1967-01-31 | Union Carbide Corp | Polyester polycarbonate polymers |
US3305605A (en) * | 1964-02-04 | 1967-02-21 | Union Carbide Corp | Compositions containing polycarbonate plasticizers |
US3312753A (en) * | 1964-01-13 | 1967-04-04 | Union Carbide Corp | Preparation of block copolymers of a caprolactone and oxirane compound |
US3378693A (en) * | 1964-07-25 | 1968-04-16 | Schmidt Metallwarenfabrik Fa G | Impulse sender for the drive of timing devices, preferably automatic permanent calendars |
US3438374A (en) * | 1966-02-28 | 1969-04-15 | Us Health Education & Welfare | Method of bonding tissue surfaces and controlling hemorrhaging thereof using a tissue adhesive and hemostatic composition |
US3442871A (en) * | 1966-05-04 | 1969-05-06 | American Cyanamid Co | Process for polymerizing a glycolide |
US3463158A (en) * | 1963-10-31 | 1969-08-26 | American Cyanamid Co | Polyglycolic acid prosthetic devices |
US3531561A (en) * | 1965-04-20 | 1970-09-29 | Ethicon Inc | Suture preparation |
US3552986A (en) * | 1967-11-24 | 1971-01-05 | Sun Chemical Corp | Printing and coating untreated polyolefins |
US3620118A (en) * | 1970-11-16 | 1971-11-16 | Yoshiyuki Koishikawa | Tambourine |
US3626948A (en) * | 1968-12-23 | 1971-12-14 | American Cyanamid Co | Absorbable polyglycolic acid suture of enhanced in-vivo strength retention |
US3629374A (en) * | 1969-04-01 | 1971-12-21 | Union Carbide Corp | Lactone/alkylene oxide copolymers as plasticizers for vinyl chloride resins |
US3639503A (en) * | 1969-02-20 | 1972-02-01 | Union Carbide Corp | Block copolycarbonates containing polylactone blocks and cyclobutylene polycarbonate blocks |
US3641200A (en) * | 1969-01-17 | 1972-02-08 | Union Carbide Corp | Block copolycarbonates containing polylactone blocks and dihydric phenol polycarbonate blocks |
US3739773A (en) * | 1963-10-31 | 1973-06-19 | American Cyanamid Co | Polyglycolic acid prosthetic devices |
DE2206144A1 (en) | 1971-10-18 | 1973-08-02 | American Cyanamid Co | COPOLYMERS ABSORBABLE BY LIVING MAMMALIAN TISSUES |
GB1332505A (en) | 1970-10-16 | 1973-10-03 | Ethicon Inc | Sutures and other surgical aids |
US3784585A (en) * | 1971-10-21 | 1974-01-08 | American Cyanamid Co | Water-degradable resins containing recurring,contiguous,polymerized glycolide units and process for preparing same |
US3795701A (en) * | 1972-02-07 | 1974-03-05 | Laporte Industries Ltd | Copolymers of epoxides and lactones |
US3839297A (en) * | 1971-11-22 | 1974-10-01 | Ethicon Inc | Use of stannous octoate catalyst in the manufacture of l(-)lactide-glycolide copolymer sutures |
US3865723A (en) * | 1972-03-21 | 1975-02-11 | Zambon Spa | Method to form stable complexes of polyanions occurring in biological liquids |
US3867190A (en) * | 1971-10-18 | 1975-02-18 | American Cyanamid Co | Reducing capillarity of polyglycolic acid sutures |
US3875937A (en) * | 1963-10-31 | 1975-04-08 | American Cyanamid Co | Surgical dressings of absorbable polymers |
US3882192A (en) * | 1973-02-01 | 1975-05-06 | Bayer Ag | Polycarbonate-polyvinyl chloride moulding compositions |
US3896802A (en) * | 1974-04-19 | 1975-07-29 | American Cyanamid Co | Flexible flocked dressing |
GB1414600A (en) | 1974-02-08 | 1975-11-19 | Ethicon Inc | Plasticised polyester sutures |
US3937223A (en) * | 1974-04-19 | 1976-02-10 | American Cyanamid Company | Compacted surgical hemostatic felt |
US3939049A (en) * | 1974-04-10 | 1976-02-17 | The United States Of America As Represented By The United States Energy Research And Development Administration | Process for radiation grafting hydrogels onto organic polymeric substrates |
US3960152A (en) * | 1974-01-21 | 1976-06-01 | American Cyanamid Company | Surgical sutures of unsymmetrically substituted 1,4-dioxane-2,5-diones |
US3966788A (en) * | 1973-10-16 | 1976-06-29 | Societe Nationale Des Poudres Et Explosifs | Process for the preparation of aliphatic diol polycarbonates |
US3981766A (en) * | 1975-02-21 | 1976-09-21 | E. I. Du Pont De Nemours And Company | Method of controlling fungi and bacteria in paper products |
US3982543A (en) * | 1973-04-24 | 1976-09-28 | American Cyanamid Company | Reducing capillarity of polyglycolic acid sutures |
US4033936A (en) * | 1974-11-15 | 1977-07-05 | Hoechst Aktiengesellschaft | Process for the manufacture of flame retarding linear polyesters |
US4045418A (en) * | 1975-01-28 | 1977-08-30 | Gulf Oil Corporation | Copolymers of D,L-lactide and epsilon caprolactone |
US4057537A (en) * | 1975-01-28 | 1977-11-08 | Gulf Oil Corporation | Copolymers of L-(-)-lactide and epsilon caprolactone |
US4066630A (en) * | 1977-01-10 | 1978-01-03 | Air Products And Chemicals, Inc. | End capped polyalkylene carbonates having improved thermal stability |
US4067876A (en) * | 1974-10-15 | 1978-01-10 | Paolo Ferruti | High polymers containing nicotinic acid, process for their preparation and their use |
US4072704A (en) * | 1974-08-19 | 1978-02-07 | Basf Wyandotte Corporation | Multi-block coupled polyoxyalkylene copolymer surfactants |
US4093677A (en) * | 1975-06-10 | 1978-06-06 | Paolo Ferruti | Macromolecular materials suitable for forming antithrombogenic prosthesis and artificial organs and process for preparing same |
US4104264A (en) * | 1977-05-05 | 1978-08-01 | Air Products & Chemicals, Inc. | End capped polyalkylene carbonates having improved thermal stablity |
US4137280A (en) * | 1978-04-19 | 1979-01-30 | Air Products And Chemicals, Inc. | Polyalkylene carbonates as processing aids for polyvinyl chloride |
US4137921A (en) * | 1977-06-24 | 1979-02-06 | Ethicon, Inc. | Addition copolymers of lactide and glycolide and method of preparation |
US4143017A (en) * | 1976-02-25 | 1979-03-06 | Hoya Lens Corporation | Process of producing soft contact lenses |
US4145525A (en) * | 1977-10-03 | 1979-03-20 | Air Products And Chemicals, Inc. | End capped polyalkylene carbonates |
US4146320A (en) * | 1976-09-08 | 1979-03-27 | Plaubel, Feinmechanik & Optik Gesellschaft Mit Beschrankter Haftung | Adjusting and latching mechanism for collapsible camera |
US4166902A (en) * | 1974-10-14 | 1979-09-04 | Paolo Ferruti | High polymers containing nicotinic acid, process for their preparation and their use |
US4169923A (en) * | 1974-10-15 | 1979-10-02 | Paolo Ferruti | High polymers containing nicotinic acid, process for their preparation and their use |
US4179304A (en) * | 1978-04-03 | 1979-12-18 | Polychrome Corporation | Finger nail lacquer |
US4189609A (en) * | 1974-08-19 | 1980-02-19 | Basf Wyandotte Corporation | Multi-block coupled polyoxyalkylene copolymer surfactants |
CA1080740A (en) | 1976-02-02 | 1980-07-01 | William K. Langdon | Multi-block coupled polyoxyalkylene copolymer surfactants |
US4211865A (en) * | 1976-08-10 | 1980-07-08 | Paolo Ferruti | Novel prostaglandin precursors in polymeric form |
US4223011A (en) * | 1974-10-15 | 1980-09-16 | Paolo Ferruti | Therapeutic compositions containing polymers having polyunsaturated acid radicals |
US4239861A (en) * | 1974-01-17 | 1980-12-16 | Bayer Aktiengesellschaft | Polyvinyl chloride-polycarbonate alloys |
US4243775A (en) * | 1978-11-13 | 1981-01-06 | American Cyanamid Company | Synthetic polyester surgical articles |
US4264425A (en) * | 1979-05-25 | 1981-04-28 | Nissan Motor Company, Limited | Device for detection of air/fuel ratio from oxygen partial pressure in exhaust gas |
US4264752A (en) * | 1979-08-08 | 1981-04-28 | Union Carbide Corporation | Radiation-curable acrylated urethane polycarbonate compositions |
US4297455A (en) * | 1977-03-22 | 1981-10-27 | Bayer Aktiengesellschaft | Process for the preparation of carbonic acid aryl esters of polyester-diols lengthened via carbonate groups and their use for the preparation of polyester-diol bis-diphenol carbonates and polyester/polycarbonates |
US4300565A (en) * | 1977-05-23 | 1981-11-17 | American Cyanamid Company | Synthetic polyester surgical articles |
US4303066A (en) * | 1979-06-28 | 1981-12-01 | National Patent Development Corporation | Burn dressing |
US4316001A (en) * | 1976-05-26 | 1982-02-16 | Societe Nationale Des Poudres Et Explosifs | Anionic polymerization of heterocyclic monomers with alkali metal amide hydroxylated compound initiator |
US4330481A (en) * | 1978-12-26 | 1982-05-18 | The Dow Chemical Company | Process for preparing polycarbonates |
US4354487A (en) * | 1980-05-12 | 1982-10-19 | Johnson & Johnson | Fiber/absorbent polymer composites and method of forming same |
US4415502A (en) * | 1980-08-11 | 1983-11-15 | The Dow Chemical Co. | Polycarbonate type nonionic surfactants |
US4429080A (en) * | 1982-07-01 | 1984-01-31 | American Cyanamid Company | Synthetic copolymer surgical articles and method of manufacturing the same |
US4436839A (en) * | 1979-08-13 | 1984-03-13 | Akzo Nv | Process for preparing polycarbonate-polyether-blockcopolymers |
US4452973A (en) * | 1982-11-12 | 1984-06-05 | American Cyanamid Company | Poly(glycolic acid)/poly(oxyethylene) triblock copolymers and method of manufacturing the same |
US4503216A (en) * | 1984-02-21 | 1985-03-05 | Eastman Kodak Company | Hydroxyl-terminated polyether-esters |
US4511478A (en) * | 1983-11-10 | 1985-04-16 | Genetic Systems Corporation | Polymerizable compounds and methods for preparing synthetic polymers that integrally contain polypeptides |
US4526938A (en) * | 1982-04-22 | 1985-07-02 | Imperial Chemical Industries Plc | Continuous release formulations |
US4559945A (en) * | 1984-09-21 | 1985-12-24 | Ethicon, Inc. | Absorbable crystalline alkylene malonate copolyesters and surgical devices therefrom |
US4632929A (en) * | 1985-01-17 | 1986-12-30 | Usv Pharmaceutical Corp. | Method of hypertensive treatment using phenyl-alkylene-2-pyridyl derivatives |
US4643191A (en) * | 1985-11-29 | 1987-02-17 | Ethicon, Inc. | Crystalline copolymers of p-dioxanone and lactide and surgical devices made therefrom |
US4653497A (en) * | 1985-11-29 | 1987-03-31 | Ethicon, Inc. | Crystalline p-dioxanone/glycolide copolymers and surgical devices made therefrom |
US4699974A (en) * | 1986-08-07 | 1987-10-13 | General Electric Company | Method of preparing copolyester carbonate from cyclic aromatic polycarbonate oligomer and lactone |
US4705820A (en) * | 1986-09-05 | 1987-11-10 | American Cyanamid Company | Surgical suture coating |
US4716203A (en) * | 1986-09-05 | 1987-12-29 | American Cyanamid Company | Diblock and triblock copolymers |
US4727134A (en) * | 1985-02-22 | 1988-02-23 | General Electric Company | Method for preparing cyclic polycarbonate oligomer mixtures |
US4741872A (en) * | 1986-05-16 | 1988-05-03 | The University Of Kentucky Research Foundation | Preparation of biodegradable microspheres useful as carriers for macromolecules |
US4745160A (en) * | 1984-06-26 | 1988-05-17 | Imperial Chemical Industries Plc | Biodegradable amphipathic copolymers |
US4760117A (en) * | 1985-06-11 | 1988-07-26 | General Electric Company | Method for preparing copolycarbonates from cyclic polycarbonate oligomers |
US4769388A (en) * | 1984-02-17 | 1988-09-06 | Nuovo Consorzio Sanitario Nazionale | Polycondensation products between 1,10-bis(2-hydroxyethylthio)decane, poly(oxyethylene glycol)s or poly(oxypropyleneglycol)s, and bis(carboxylic acid)s |
US4768523A (en) * | 1981-04-29 | 1988-09-06 | Lifecore Biomedical, Inc. | Hydrogel adhesive |
US4781183A (en) | 1986-08-27 | 1988-11-01 | American Cyanamid Company | Surgical prosthesis |
US4788879A (en) | 1987-09-17 | 1988-12-06 | Ulrich Dana L | Apparatus for hand operation of throttle and brake pedal, and methods of constructing and utilizing same |
US4791929A (en) | 1986-09-23 | 1988-12-20 | American Cyanamid Company | Bioabsorbable coating for a surgical article |
US4804691A (en) | 1987-08-28 | 1989-02-14 | Richards Medical Company | Method for making a biodegradable adhesive for soft living tissue |
US4826945A (en) | 1987-06-09 | 1989-05-02 | Yissum Research Development Company | Biodegradable polymeric materials based on polyether glycols, processes for the preparation thereof and surgical articles made therefrom |
US4846165A (en) | 1986-11-26 | 1989-07-11 | Dentsply Research & Development Corp. | Wound dressing membrane |
US4867602A (en) | 1988-06-17 | 1989-09-19 | Courtoise Robert L | Attachment for cleaning and refacing concrete joints |
US4882168A (en) | 1986-09-05 | 1989-11-21 | American Cyanamid Company | Polyesters containing alkylene oxide blocks as drug delivery systems |
US4891263A (en) | 1987-12-17 | 1990-01-02 | Allied-Signal Inc. | Polycarbonate random copolymer-based fiber compositions and method of melt-spinning same and device |
US4900797A (en) | 1988-03-17 | 1990-02-13 | Bayer Aktiengesellschaft | Thermoplastic polycarbonate mixtures containing aliphatic |
US4916193A (en) | 1987-12-17 | 1990-04-10 | Allied-Signal Inc. | Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides |
US4920203A (en) | 1987-12-17 | 1990-04-24 | Allied-Signal Inc. | Medical devices fabricated from homopolymers and copolymers having recurring carbonate units |
US4929750A (en) | 1984-02-17 | 1990-05-29 | Nuovo Consorzio Sanitario Nazionale | Compounds having hypolipemizing activity |
US4938763A (en) | 1988-10-03 | 1990-07-03 | Dunn Richard L | Biodegradable in-situ forming implants and methods of producing the same |
US4944767A (en) | 1986-01-16 | 1990-07-31 | G. Creamascoli S.P.A. | Synthetic material apt to stably adsorb high quantities of heparin, and process for the production thereof |
US4960866A (en) | 1986-12-06 | 1990-10-02 | Boehringer Ingelheim Zentrale | Catalyst-free resorbable homopolymers and copolymers |
US4961890A (en) | 1986-08-08 | 1990-10-09 | Ethypharm | Method of preparing comtrolled release fenofibrate |
US4965300A (en) | 1987-01-06 | 1990-10-23 | Bayer Aktiengesellschaft | Sequential copolymers based on cyclic carbonates and esters |
US4997722A (en) | 1989-07-10 | 1991-03-05 | Edward Adler | Composition and method for improving adherence of copper foil to resinous substrates |
US5009224A (en) | 1986-09-30 | 1991-04-23 | Minnesota Mining And Manufacturing Company | Method for attaching a pressure-sensitive film article having high moisture vapor transmission rate |
US5019094A (en) | 1990-05-09 | 1991-05-28 | Ethicon, Inc. | Crystalline copolymers of p-dioxanone and poly(alkylene oxides) |
US5019100A (en) | 1987-07-01 | 1991-05-28 | Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno | Use of a polymer network, method for preparing a prepolymer and also preparation which yields a polymer network after curing |
US5043398A (en) | 1989-05-12 | 1991-08-27 | Hoechst Celanese Corporation | Grafting of functional compounds onto functional oxymethylene polymer backbones, with diisocyanate coupling agents, and the graft polymers thereof |
US5051272A (en) | 1988-07-19 | 1991-09-24 | United States Surgical Corporation | Method for improving the storage stability of a polymeric article susceptible to hydrolytic degradation and resulting article |
US5061281A (en) | 1985-12-17 | 1991-10-29 | Allied-Signal Inc. | Bioresorbable polymers and implantation devices thereof |
US5066772A (en) | 1987-12-17 | 1991-11-19 | Allied-Signal Inc. | Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides |
US5067961A (en) | 1988-02-18 | 1991-11-26 | Autogenesis Technologies, Inc. | Non-biodegradable two phase corneal implant and method for preparing same |
US5076807A (en) | 1989-07-31 | 1991-12-31 | Ethicon, Inc. | Random copolymers of p-dioxanone, lactide and/or glycolide as coating polymers for surgical filaments |
US5081224A (en) | 1989-10-16 | 1992-01-14 | Kanegafuchi Chemical Industry Co., Ltd. | Process for production of olefin-terminated polyesters |
US5100992A (en) | 1989-05-04 | 1992-03-31 | Biomedical Polymers International, Ltd. | Polyurethane-based polymeric materials and biomedical articles and pharmaceutical compositions utilizing the same |
US5104957A (en) | 1990-02-28 | 1992-04-14 | Autogenesis Technologies, Inc. | Biologically compatible collagenous reaction product and articles useful as medical implants produced therefrom |
US5116929A (en) | 1988-10-14 | 1992-05-26 | Enichem Synthesis S.P.A. | Copolyester-diol polycarbonates, process for producing them and their use |
US5120802A (en) | 1987-12-17 | 1992-06-09 | Allied-Signal Inc. | Polycarbonate-based block copolymers and devices |
EP0258749B1 (en) | 1986-09-05 | 1992-06-17 | American Cyanamid Company | Surgical filament coating |
US5137800A (en) | 1989-02-24 | 1992-08-11 | Stereographics Limited Partnership | Production of three dimensional bodies by photopolymerization |
US5146945A (en) | 1989-12-06 | 1992-09-15 | Westinghouse Electric Corp. | Seal ring retainer and guide ring for valve plug |
US5147698A (en) | 1986-09-30 | 1992-09-15 | Minnesota Mining And Manufacturing Company | Pressure sensitive adhesive film article having high moisture vapor transmission rate |
US5152781A (en) | 1987-12-17 | 1992-10-06 | Allied-Signal Inc. | Medical devices fabricated from homopolymers and copolymers having recurring carbonate units |
US5156613A (en) | 1991-02-13 | 1992-10-20 | Interface Biomedical Laboratories Corp. | Collagen welding rod material for use in tissue welding |
US5160745A (en) | 1986-05-16 | 1992-11-03 | The University Of Kentucky Research Foundation | Biodegradable microspheres as a carrier for macromolecules |
US5173301A (en) | 1990-11-27 | 1992-12-22 | Sanyo Chemical Industries, Ltd. | Surgical adhesive |
US5177120A (en) | 1984-07-31 | 1993-01-05 | Dentsply Research & Development Corp. | Chain extended urethane diacrylate and dental impression formation |
US5201764A (en) | 1990-02-28 | 1993-04-13 | Autogenesis Technologies, Inc. | Biologically compatible collagenous reaction product and articles useful as medical implants produced therefrom |
US5209776A (en) | 1990-07-27 | 1993-05-11 | The Trustees Of Columbia University In The City Of New York | Tissue bonding and sealing composition and method of using the same |
US5225129A (en) | 1990-07-19 | 1993-07-06 | Dsm N.V. | Method for the manufacture of polymer products from cyclic esters |
US5226877A (en) | 1989-06-23 | 1993-07-13 | Epstein Gordon H | Method and apparatus for preparing fibrinogen adhesive from whole blood |
US5252701A (en) | 1990-07-06 | 1993-10-12 | American Cyanamid Company | Segmented absorbable copolymer |
US5256764A (en) | 1987-12-17 | 1993-10-26 | United States Surgical Corporation | Medical devices fabricated from homopolymers and copolymers having recurring carbonate units |
US5264425A (en) | 1988-06-03 | 1993-11-23 | Italfarmaco S.P.A. | Glycosaminoglycan salts and pharmaceutical compositions containing them |
US5274074A (en) | 1987-12-17 | 1993-12-28 | United States Surgical Corporation | Medical devices fabricated from homopolymers and copolymers having recurring carbonate units |
US5278200A (en) | 1992-10-30 | 1994-01-11 | Medtronic, Inc. | Thromboresistant material and articles |
US5296627A (en) | 1988-06-20 | 1994-03-22 | Ppg Industries, Inc. | Ethylenically unsaturated poly(alkyleneoxy) surfactants |
US5308887A (en) | 1991-05-23 | 1994-05-03 | Minnesota Mining & Manufacturing Company | Pressure-sensitive adhesives |
US5310599A (en) | 1993-05-06 | 1994-05-10 | E. I. Du Pont De Nemours And Company | Method for making polymers of alpha-hydroxy acids |
US5324307A (en) | 1990-07-06 | 1994-06-28 | American Cyanamid Company | Polymeric surgical staple |
US5332802A (en) | 1988-02-18 | 1994-07-26 | Autogenesis Technologies, Inc. | Human collagen processing and autoimplant use |
US5332475A (en) | 1989-08-02 | 1994-07-26 | University Of North Carolina At Chapel Hill | Cross-linking collagenous product |
US5354336A (en) | 1991-01-29 | 1994-10-11 | Autogenesis Technologies, Inc. | Method for bonding soft tissue with collagen-based adhesives and sealants |
US5359026A (en) | 1993-07-30 | 1994-10-25 | Cargill, Incorporated | Poly(lactide) copolymer and process for manufacture thereof |
US5360892A (en) | 1990-06-26 | 1994-11-01 | Arch Development Corporation | Water and UV degradable lactic acid polymers |
US5364700A (en) | 1985-12-27 | 1994-11-15 | Amoco Corporation | Prepregable resin composition and composite |
US5366756A (en) | 1992-06-15 | 1994-11-22 | United States Surgical Corporation | Method for treating bioabsorbable implant material |
US5372585A (en) | 1992-04-09 | 1994-12-13 | Tiefenbrun; Jonathan | Instrument and associated method for applying biologically effective composition during laparoscopic operation |
US5378801A (en) | 1988-11-01 | 1995-01-03 | Reichert; Dieter | Continuous process for the preparation of resorable polyesters and the use thereof |
US5385606A (en) | 1992-07-06 | 1995-01-31 | Kowanko; Nicholas | Adhesive composition and method |
US5391707A (en) | 1993-12-10 | 1995-02-21 | United States Surgical Corporation | Process for the production of dioxanone |
US5397816A (en) | 1992-11-17 | 1995-03-14 | Ethicon, Inc. | Reinforced absorbable polymers |
US5403347A (en) | 1993-05-27 | 1995-04-04 | United States Surgical Corporation | Absorbable block copolymers and surgical articles fabricated therefrom |
US5403826A (en) | 1993-05-28 | 1995-04-04 | Abbott Laboratories | Nutritional product for persons infected with human immunodeficiency virus |
US5410016A (en) | 1990-10-15 | 1995-04-25 | Board Of Regents, The University Of Texas System | Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers |
US5412067A (en) | 1993-05-10 | 1995-05-02 | Mitsui Toatsu Chemicals, Inc. | Preparation process of polyester |
US5425984A (en) | 1991-07-19 | 1995-06-20 | United States Surgical Corporation | Bioabsorbable melt spun fiber based on glycolide-containing copolymer |
US5447966A (en) | 1988-07-19 | 1995-09-05 | United States Surgical Corporation | Treating bioabsorbable surgical articles by coating with glycerine, polalkyleneoxide block copolymer and gelatin |
US5449743A (en) | 1993-01-29 | 1995-09-12 | Shiro Kobayashi | Method for ring opening polymerization using a hydrolase catalyst |
US5459177A (en) | 1993-03-09 | 1995-10-17 | Sun Medical Co., Ltd. | Adhesive for soft tissue and kit thereof |
US5463012A (en) | 1991-06-14 | 1995-10-31 | Mediolanum Farmaceutici S.P.A. | Polycarbonates and the use thereof for the preparation of bioerosible matrices |
US5468253A (en) | 1993-01-21 | 1995-11-21 | Ethicon, Inc. | Elastomeric medical device |
US5476516A (en) | 1992-03-13 | 1995-12-19 | Albert Einstein College Of Medicine Of Yeshiva University | Anticalcification treatment for aldehyde-tanned biological tissue |
US5478921A (en) | 1994-08-25 | 1995-12-26 | United States Surgical Corporation | Method of purifying bioabsorable polymer |
US5484913A (en) | 1993-12-23 | 1996-01-16 | Johnson & Johnson Medical, Inc. | Calcium-modified oxidized cellulose hemostat |
US5496872A (en) | 1993-07-21 | 1996-03-05 | Imedex | Adhesive compositions for surgical use |
US5502158A (en) | 1988-08-08 | 1996-03-26 | Ecopol, Llc | Degradable polymer composition |
US5508317A (en) | 1993-08-06 | 1996-04-16 | Ciba-Geigy Corporation | Photocrosslinked polymers |
US5512091A (en) | 1990-08-13 | 1996-04-30 | Steiner; Carol A. | Associative polymer hydrogels |
US5516825A (en) | 1992-08-13 | 1996-05-14 | Zeneca Limited | Biodegradable polymer compositions |
US5522841A (en) | 1993-05-27 | 1996-06-04 | United States Surgical Corporation | Absorbable block copolymers and surgical articles fabricated therefrom |
US5525646A (en) | 1991-03-04 | 1996-06-11 | Lundgren; Dan | Bioresorbable material and an article of manufacture made of such material for medical use |
US5525647A (en) | 1994-08-01 | 1996-06-11 | American Dental Association Health Foundation | Method and device for controllably affecting the reaction of dental adhesives |
US5527864A (en) | 1995-08-08 | 1996-06-18 | Suggs; Laura J. | Poly(propylene fumarate-co-ethylene oxide) |
US5529914A (en) | 1990-10-15 | 1996-06-25 | The Board Of Regents The Univeristy Of Texas System | Gels for encapsulation of biological materials |
US5530038A (en) | 1993-08-02 | 1996-06-25 | Sun Medical Co., Ltd. | Primer composition and curable composition |
US5531707A (en) | 1990-06-08 | 1996-07-02 | Ab Astra | Device for introducing a substance into a body cavity of a patient |
US5531709A (en) | 1993-09-23 | 1996-07-02 | Heraeus Kulzer Gmbh | Syringe for the controlled discharge of viscous materials |
US5540677A (en) | 1990-06-15 | 1996-07-30 | Rare Earth Medical, Inc. | Endoscopic systems for photoreactive suturing of biological materials |
US5550209A (en) | 1994-03-04 | 1996-08-27 | Daicel Chemical Industries, Ltd. | Monodispersed polymer or copolymer and a preparation process thereof |
US5552452A (en) | 1993-03-15 | 1996-09-03 | Arch Development Corp. | Organic tissue glue for closure of wounds |
US5554665A (en) | 1993-06-23 | 1996-09-10 | Dentsply Research & Development Corp. | Method and dispenser for making dental products |
US5561157A (en) | 1986-12-23 | 1996-10-01 | Tristrata Inc | Method for enhancing the therapeutic effect of a composition comprising hydroquinone and comprising same |
US5563238A (en) | 1993-08-05 | 1996-10-08 | Arch Development Corporation | Water and UV degradable lactic acid polymers |
US5567435A (en) | 1992-02-28 | 1996-10-22 | Board Of Regents, The University Of Texas System | Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers |
US5573934A (en) | 1992-04-20 | 1996-11-12 | Board Of Regents, The University Of Texas System | Gels for encapsulation of biological materials |
US5589563A (en) | 1992-04-24 | 1996-12-31 | The Polymer Technology Group | Surface-modifying endgroups for biomedical polymers |
US5607686A (en) | 1994-11-22 | 1997-03-04 | United States Surgical Corporation | Polymeric composition |
US5621119A (en) | 1994-07-22 | 1997-04-15 | Heraeus Kulzer Gmbh & Co., Kg | Di(meth)acrylates having cyclic carbonate groups |
US5621050A (en) | 1992-03-02 | 1997-04-15 | American Cyanamid Company | Coating for tissue drag reduction |
US5629384A (en) | 1994-05-17 | 1997-05-13 | Consiglio Nazionale Delle Ricerche | Polymers of N-acryloylmorpholine activated at one end and conjugates with bioactive materials and surfaces |
US5631336A (en) | 1992-08-27 | 1997-05-20 | Consiglio Nazionale Delle Ricerche | Chain-terminated N-vinyl lactam polymers and graft-copolymers and methods for making same |
US5633342A (en) | 1995-10-27 | 1997-05-27 | Chronopol, Inc. | Method for the synthesis of environmentally degradable block copolymers |
US5650234A (en) | 1994-09-09 | 1997-07-22 | Surface Engineering Technologies, Division Of Innerdyne, Inc. | Electrophilic polyethylene oxides for the modification of polysaccharides, polypeptides (proteins) and surfaces |
US5658995A (en) | 1995-11-27 | 1997-08-19 | Rutgers, The State University | Copolymers of tyrosine-based polycarbonate and poly(alkylene oxide) |
US5665428A (en) | 1995-10-25 | 1997-09-09 | Macromed, Inc. | Preparation of peptide containing biodegradable microspheres by melt process |
US5665474A (en) | 1992-10-02 | 1997-09-09 | Cargill, Incorporated | Paper having a melt-stable lactide polymer coating and process for manufacture thereof |
US5698661A (en) | 1993-11-05 | 1997-12-16 | Asta Medica Aktiengesellschaft | High molecular weight polyesterpolycarbonates and the use thereof for the preparation of bioerosible matrices |
US5698213A (en) | 1995-03-06 | 1997-12-16 | Ethicon, Inc. | Hydrogels of absorbable polyoxaesters |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2517965A (en) | 1948-03-23 | 1950-08-08 | Pittsburgh Plate Glass Co | Purification of carbonic acid esters |
US3063988A (en) | 1959-11-14 | 1962-11-13 | Hoechst Ag | Steroid-21-amino acid esters and process of preparing them |
US3379693A (en) | 1964-05-28 | 1968-04-23 | Union Carbide Corp | Carbonate compositions |
US3991766A (en) | 1973-05-31 | 1976-11-16 | American Cyanamid Company | Controlled release of medicaments using polymers from glycolic acid |
US4033938A (en) | 1974-01-21 | 1977-07-05 | American Cyanamid Company | Polymers of unsymmetrically substituted 1,4-dioxane-2,5-diones |
US4145320A (en) | 1974-10-15 | 1979-03-20 | Paolo Ferruti | Polymers containing polyunsaturated acid radicals, process for their preparation and use thereof |
US4079038A (en) | 1976-03-05 | 1978-03-14 | Alza Corporation | Poly(carbonates) |
DE2850824C2 (en) | 1978-05-17 | 1995-03-16 | American Cyanamid Co | Surgical articles and process for their preparation |
US4532929A (en) | 1984-07-23 | 1985-08-06 | Ethicon, Inc. | Dry coating of surgical filaments |
US4857602A (en) | 1986-09-05 | 1989-08-15 | American Cyanamid Company | Bioabsorbable surgical suture coating |
US4788979A (en) | 1986-09-23 | 1988-12-06 | American Cyanamid Company | Bioabsorbable coating for a surgical article |
JP2868817B2 (en) | 1987-12-17 | 1999-03-10 | ユナイテッド・ステーツ・サージカル・コーポレーション | Medical devices made from homopolymers and copolymers containing repeating carbonate units |
US5145945A (en) | 1987-12-17 | 1992-09-08 | Allied-Signal Inc. | Homopolymers and copolymers having recurring carbonate units |
CA2002016A1 (en) | 1988-11-21 | 1990-05-21 | Koji Miyake | Manufacturing method, continuous manufacturing method, product and manufacturing apparatus of absorbent composite |
US5403626A (en) | 1990-09-27 | 1995-04-04 | Sam Yang Co., Limited | Process for preparing hydrophilic polymer films and apparatus thereof |
WO1993002639A1 (en) | 1991-08-06 | 1993-02-18 | Autogenesis Technologies, Inc. | Injectable collagen-based compositions for making intraocular lens |
CA2114290C (en) | 1993-01-27 | 2006-01-10 | Nagabushanam Totakura | Post-surgical anti-adhesion device |
JP3399573B2 (en) | 1993-01-29 | 2003-04-21 | 株式会社ジーシー | Tooth surface treatment kit |
US5612052A (en) | 1995-04-13 | 1997-03-18 | Poly-Med, Inc. | Hydrogel-forming, self-solvating absorbable polyester copolymers, and methods for use thereof |
US5837752A (en) | 1997-07-17 | 1998-11-17 | Massachusetts Institute Of Technology | Semi-interpenetrating polymer networks |
EP1586349A1 (en) * | 2000-12-27 | 2005-10-19 | Genzyme Corporation | Controlled release of anti-arrhythmic agents |
-
1997
- 1997-09-23 ZA ZA9708537A patent/ZA978537B/en unknown
- 1997-10-06 US US08/944,739 patent/US6083524A/en not_active Expired - Lifetime
-
2000
- 2000-01-07 US US09/479,520 patent/US6177095B1/en not_active Ceased
-
2003
- 2003-01-23 US US10/351,930 patent/USRE39713E1/en not_active Expired - Lifetime
Patent Citations (227)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2155658A (en) * | 1936-01-08 | 1939-04-25 | Chemische Forschungs Gmbh | Surgical and medical preparations |
US2210817A (en) * | 1939-04-19 | 1940-08-06 | Du Pont | Superpolycarbonate |
US2517985A (en) * | 1948-06-22 | 1950-08-08 | Malcom A Davis | Chimney for liquid fuel burners |
US2683136A (en) * | 1950-10-25 | 1954-07-06 | Du Pont | Copolymers of hydroxyacetic acid with other alcohol acids |
US2703316A (en) * | 1951-06-05 | 1955-03-01 | Du Pont | Polymers of high melting lactide |
US2668162A (en) * | 1952-03-20 | 1954-02-02 | Du Pont | Preparation of high molecular weight polyhydroxyacetic ester |
US2789968A (en) * | 1953-12-08 | 1957-04-23 | Eastman Kodak Co | Polycarbonates from polymethylene glycol-bis |
US2917410A (en) * | 1955-06-20 | 1959-12-15 | American Cyanamid Co | Polyglycol-polyacid ester treatment of textiles |
US3161615A (en) * | 1957-02-05 | 1964-12-15 | Gen Electric | Resinous copolymeric polycarbonate of a mixture of dihydric phenols |
US2962524A (en) * | 1957-04-18 | 1960-11-29 | Chich | |
US3046255A (en) * | 1957-06-20 | 1962-07-24 | Pittsburgh Plate Glass Co | Process for preparing polycarbonates |
US3169121A (en) * | 1957-08-22 | 1965-02-09 | Gen Electric | Carbonate-carboxylate copolyesters of dihydric phenols and difunctional carboxylic acids |
US3030331A (en) * | 1957-08-22 | 1962-04-17 | Gen Electric | Process for preparing copolyesters comprising reacting a carbonyl halide with a dicarboxylic acid and a dihydroxy compound in the presence of a tertiary amine |
GB965085A (en) | 1959-07-17 | 1964-07-29 | Eastman Kodak Co | Block copolycarbonates |
US3021310A (en) * | 1959-12-03 | 1962-02-13 | Union Garbide Corp | Polymerization of cyclic esters |
US3063968A (en) * | 1960-06-15 | 1962-11-13 | Gen Aniline & Film Corp | Polymerization of 2-p-dioxanone |
US3223083A (en) * | 1960-09-09 | 1965-12-14 | President And Directors Of Geo | Method for adhesively securing together skin and other soft tissue and bone |
US3157622A (en) * | 1961-01-03 | 1964-11-17 | Gen Electric | Resinous compositions |
US3268486A (en) * | 1963-06-28 | 1966-08-23 | Shell Oil Co | Process for preparing polyesters |
US3301825A (en) * | 1963-09-26 | 1967-01-31 | Union Carbide Corp | Polyester polycarbonate polymers |
US3301824A (en) * | 1963-09-26 | 1967-01-31 | Union Carbide Corp | Polymers of cyclic carbonates |
US3297033A (en) * | 1963-10-31 | 1967-01-10 | American Cyanamid Co | Surgical sutures |
US3875937A (en) * | 1963-10-31 | 1975-04-08 | American Cyanamid Co | Surgical dressings of absorbable polymers |
US3739773A (en) * | 1963-10-31 | 1973-06-19 | American Cyanamid Co | Polyglycolic acid prosthetic devices |
US3463158A (en) * | 1963-10-31 | 1969-08-26 | American Cyanamid Co | Polyglycolic acid prosthetic devices |
US3268487A (en) * | 1963-12-23 | 1966-08-23 | Shell Oil Co | Process for polymerization of lactides |
US3312753A (en) * | 1964-01-13 | 1967-04-04 | Union Carbide Corp | Preparation of block copolymers of a caprolactone and oxirane compound |
US3305605A (en) * | 1964-02-04 | 1967-02-21 | Union Carbide Corp | Compositions containing polycarbonate plasticizers |
US3378693A (en) * | 1964-07-25 | 1968-04-16 | Schmidt Metallwarenfabrik Fa G | Impulse sender for the drive of timing devices, preferably automatic permanent calendars |
US3531561A (en) * | 1965-04-20 | 1970-09-29 | Ethicon Inc | Suture preparation |
US3438374A (en) * | 1966-02-28 | 1969-04-15 | Us Health Education & Welfare | Method of bonding tissue surfaces and controlling hemorrhaging thereof using a tissue adhesive and hemostatic composition |
US3442871A (en) * | 1966-05-04 | 1969-05-06 | American Cyanamid Co | Process for polymerizing a glycolide |
US3552986A (en) * | 1967-11-24 | 1971-01-05 | Sun Chemical Corp | Printing and coating untreated polyolefins |
US3626948A (en) * | 1968-12-23 | 1971-12-14 | American Cyanamid Co | Absorbable polyglycolic acid suture of enhanced in-vivo strength retention |
US3641200A (en) * | 1969-01-17 | 1972-02-08 | Union Carbide Corp | Block copolycarbonates containing polylactone blocks and dihydric phenol polycarbonate blocks |
US3639503A (en) * | 1969-02-20 | 1972-02-01 | Union Carbide Corp | Block copolycarbonates containing polylactone blocks and cyclobutylene polycarbonate blocks |
US3629374A (en) * | 1969-04-01 | 1971-12-21 | Union Carbide Corp | Lactone/alkylene oxide copolymers as plasticizers for vinyl chloride resins |
GB1332505A (en) | 1970-10-16 | 1973-10-03 | Ethicon Inc | Sutures and other surgical aids |
US3620118A (en) * | 1970-11-16 | 1971-11-16 | Yoshiyuki Koishikawa | Tambourine |
US3867190A (en) * | 1971-10-18 | 1975-02-18 | American Cyanamid Co | Reducing capillarity of polyglycolic acid sutures |
DE2206144A1 (en) | 1971-10-18 | 1973-08-02 | American Cyanamid Co | COPOLYMERS ABSORBABLE BY LIVING MAMMALIAN TISSUES |
US3784585A (en) * | 1971-10-21 | 1974-01-08 | American Cyanamid Co | Water-degradable resins containing recurring,contiguous,polymerized glycolide units and process for preparing same |
US3839297A (en) * | 1971-11-22 | 1974-10-01 | Ethicon Inc | Use of stannous octoate catalyst in the manufacture of l(-)lactide-glycolide copolymer sutures |
US3795701A (en) * | 1972-02-07 | 1974-03-05 | Laporte Industries Ltd | Copolymers of epoxides and lactones |
US3865723A (en) * | 1972-03-21 | 1975-02-11 | Zambon Spa | Method to form stable complexes of polyanions occurring in biological liquids |
US3882192A (en) * | 1973-02-01 | 1975-05-06 | Bayer Ag | Polycarbonate-polyvinyl chloride moulding compositions |
US3982543A (en) * | 1973-04-24 | 1976-09-28 | American Cyanamid Company | Reducing capillarity of polyglycolic acid sutures |
US3966788A (en) * | 1973-10-16 | 1976-06-29 | Societe Nationale Des Poudres Et Explosifs | Process for the preparation of aliphatic diol polycarbonates |
US4239861A (en) * | 1974-01-17 | 1980-12-16 | Bayer Aktiengesellschaft | Polyvinyl chloride-polycarbonate alloys |
US3960152A (en) * | 1974-01-21 | 1976-06-01 | American Cyanamid Company | Surgical sutures of unsymmetrically substituted 1,4-dioxane-2,5-diones |
GB1414600A (en) | 1974-02-08 | 1975-11-19 | Ethicon Inc | Plasticised polyester sutures |
US3939049A (en) * | 1974-04-10 | 1976-02-17 | The United States Of America As Represented By The United States Energy Research And Development Administration | Process for radiation grafting hydrogels onto organic polymeric substrates |
US3896802A (en) * | 1974-04-19 | 1975-07-29 | American Cyanamid Co | Flexible flocked dressing |
US3937223A (en) * | 1974-04-19 | 1976-02-10 | American Cyanamid Company | Compacted surgical hemostatic felt |
US4072704A (en) * | 1974-08-19 | 1978-02-07 | Basf Wyandotte Corporation | Multi-block coupled polyoxyalkylene copolymer surfactants |
US4189609A (en) * | 1974-08-19 | 1980-02-19 | Basf Wyandotte Corporation | Multi-block coupled polyoxyalkylene copolymer surfactants |
US4166902A (en) * | 1974-10-14 | 1979-09-04 | Paolo Ferruti | High polymers containing nicotinic acid, process for their preparation and their use |
US4067876A (en) * | 1974-10-15 | 1978-01-10 | Paolo Ferruti | High polymers containing nicotinic acid, process for their preparation and their use |
US4169923A (en) * | 1974-10-15 | 1979-10-02 | Paolo Ferruti | High polymers containing nicotinic acid, process for their preparation and their use |
US4223011A (en) * | 1974-10-15 | 1980-09-16 | Paolo Ferruti | Therapeutic compositions containing polymers having polyunsaturated acid radicals |
US4033936A (en) * | 1974-11-15 | 1977-07-05 | Hoechst Aktiengesellschaft | Process for the manufacture of flame retarding linear polyesters |
US4045418A (en) * | 1975-01-28 | 1977-08-30 | Gulf Oil Corporation | Copolymers of D,L-lactide and epsilon caprolactone |
US4057537A (en) * | 1975-01-28 | 1977-11-08 | Gulf Oil Corporation | Copolymers of L-(-)-lactide and epsilon caprolactone |
US3981766A (en) * | 1975-02-21 | 1976-09-21 | E. I. Du Pont De Nemours And Company | Method of controlling fungi and bacteria in paper products |
US4093677A (en) * | 1975-06-10 | 1978-06-06 | Paolo Ferruti | Macromolecular materials suitable for forming antithrombogenic prosthesis and artificial organs and process for preparing same |
CA1080740A (en) | 1976-02-02 | 1980-07-01 | William K. Langdon | Multi-block coupled polyoxyalkylene copolymer surfactants |
US4143017A (en) * | 1976-02-25 | 1979-03-06 | Hoya Lens Corporation | Process of producing soft contact lenses |
US4316001A (en) * | 1976-05-26 | 1982-02-16 | Societe Nationale Des Poudres Et Explosifs | Anionic polymerization of heterocyclic monomers with alkali metal amide hydroxylated compound initiator |
US4211865A (en) * | 1976-08-10 | 1980-07-08 | Paolo Ferruti | Novel prostaglandin precursors in polymeric form |
US4146320A (en) * | 1976-09-08 | 1979-03-27 | Plaubel, Feinmechanik & Optik Gesellschaft Mit Beschrankter Haftung | Adjusting and latching mechanism for collapsible camera |
US4066630A (en) * | 1977-01-10 | 1978-01-03 | Air Products And Chemicals, Inc. | End capped polyalkylene carbonates having improved thermal stability |
US4297455A (en) * | 1977-03-22 | 1981-10-27 | Bayer Aktiengesellschaft | Process for the preparation of carbonic acid aryl esters of polyester-diols lengthened via carbonate groups and their use for the preparation of polyester-diol bis-diphenol carbonates and polyester/polycarbonates |
US4104264A (en) * | 1977-05-05 | 1978-08-01 | Air Products & Chemicals, Inc. | End capped polyalkylene carbonates having improved thermal stablity |
US4300565A (en) * | 1977-05-23 | 1981-11-17 | American Cyanamid Company | Synthetic polyester surgical articles |
US4137921A (en) * | 1977-06-24 | 1979-02-06 | Ethicon, Inc. | Addition copolymers of lactide and glycolide and method of preparation |
US4157437A (en) * | 1977-06-24 | 1979-06-05 | Ethicon, Inc. | Addition copolymers of lactide and glycolide and method of preparation |
US4145525A (en) * | 1977-10-03 | 1979-03-20 | Air Products And Chemicals, Inc. | End capped polyalkylene carbonates |
US4179304A (en) * | 1978-04-03 | 1979-12-18 | Polychrome Corporation | Finger nail lacquer |
US4137280A (en) * | 1978-04-19 | 1979-01-30 | Air Products And Chemicals, Inc. | Polyalkylene carbonates as processing aids for polyvinyl chloride |
US4243775A (en) * | 1978-11-13 | 1981-01-06 | American Cyanamid Company | Synthetic polyester surgical articles |
US4330481A (en) * | 1978-12-26 | 1982-05-18 | The Dow Chemical Company | Process for preparing polycarbonates |
US4264425A (en) * | 1979-05-25 | 1981-04-28 | Nissan Motor Company, Limited | Device for detection of air/fuel ratio from oxygen partial pressure in exhaust gas |
US4303066A (en) * | 1979-06-28 | 1981-12-01 | National Patent Development Corporation | Burn dressing |
US4264752A (en) * | 1979-08-08 | 1981-04-28 | Union Carbide Corporation | Radiation-curable acrylated urethane polycarbonate compositions |
US4436839A (en) * | 1979-08-13 | 1984-03-13 | Akzo Nv | Process for preparing polycarbonate-polyether-blockcopolymers |
US4354487A (en) * | 1980-05-12 | 1982-10-19 | Johnson & Johnson | Fiber/absorbent polymer composites and method of forming same |
US4415502A (en) * | 1980-08-11 | 1983-11-15 | The Dow Chemical Co. | Polycarbonate type nonionic surfactants |
US4768523A (en) * | 1981-04-29 | 1988-09-06 | Lifecore Biomedical, Inc. | Hydrogel adhesive |
US4526938A (en) * | 1982-04-22 | 1985-07-02 | Imperial Chemical Industries Plc | Continuous release formulations |
US4942035A (en) | 1982-04-22 | 1990-07-17 | Imperial Chemical Industries | Continuous release formulations |
US4429080A (en) * | 1982-07-01 | 1984-01-31 | American Cyanamid Company | Synthetic copolymer surgical articles and method of manufacturing the same |
US4452973A (en) * | 1982-11-12 | 1984-06-05 | American Cyanamid Company | Poly(glycolic acid)/poly(oxyethylene) triblock copolymers and method of manufacturing the same |
US4511478A (en) * | 1983-11-10 | 1985-04-16 | Genetic Systems Corporation | Polymerizable compounds and methods for preparing synthetic polymers that integrally contain polypeptides |
US4929750A (en) | 1984-02-17 | 1990-05-29 | Nuovo Consorzio Sanitario Nazionale | Compounds having hypolipemizing activity |
US4769388A (en) * | 1984-02-17 | 1988-09-06 | Nuovo Consorzio Sanitario Nazionale | Polycondensation products between 1,10-bis(2-hydroxyethylthio)decane, poly(oxyethylene glycol)s or poly(oxypropyleneglycol)s, and bis(carboxylic acid)s |
US4503216A (en) * | 1984-02-21 | 1985-03-05 | Eastman Kodak Company | Hydroxyl-terminated polyether-esters |
US4745160A (en) * | 1984-06-26 | 1988-05-17 | Imperial Chemical Industries Plc | Biodegradable amphipathic copolymers |
US5177120A (en) | 1984-07-31 | 1993-01-05 | Dentsply Research & Development Corp. | Chain extended urethane diacrylate and dental impression formation |
US4559945A (en) * | 1984-09-21 | 1985-12-24 | Ethicon, Inc. | Absorbable crystalline alkylene malonate copolyesters and surgical devices therefrom |
US4632929A (en) * | 1985-01-17 | 1986-12-30 | Usv Pharmaceutical Corp. | Method of hypertensive treatment using phenyl-alkylene-2-pyridyl derivatives |
US4727134A (en) * | 1985-02-22 | 1988-02-23 | General Electric Company | Method for preparing cyclic polycarbonate oligomer mixtures |
US4760117A (en) * | 1985-06-11 | 1988-07-26 | General Electric Company | Method for preparing copolycarbonates from cyclic polycarbonate oligomers |
US4653497A (en) * | 1985-11-29 | 1987-03-31 | Ethicon, Inc. | Crystalline p-dioxanone/glycolide copolymers and surgical devices made therefrom |
US4643191A (en) * | 1985-11-29 | 1987-02-17 | Ethicon, Inc. | Crystalline copolymers of p-dioxanone and lactide and surgical devices made therefrom |
US5061281A (en) | 1985-12-17 | 1991-10-29 | Allied-Signal Inc. | Bioresorbable polymers and implantation devices thereof |
US5364700A (en) | 1985-12-27 | 1994-11-15 | Amoco Corporation | Prepregable resin composition and composite |
US4944767A (en) | 1986-01-16 | 1990-07-31 | G. Creamascoli S.P.A. | Synthetic material apt to stably adsorb high quantities of heparin, and process for the production thereof |
US5160745A (en) | 1986-05-16 | 1992-11-03 | The University Of Kentucky Research Foundation | Biodegradable microspheres as a carrier for macromolecules |
US4741872A (en) * | 1986-05-16 | 1988-05-03 | The University Of Kentucky Research Foundation | Preparation of biodegradable microspheres useful as carriers for macromolecules |
US4699974A (en) * | 1986-08-07 | 1987-10-13 | General Electric Company | Method of preparing copolyester carbonate from cyclic aromatic polycarbonate oligomer and lactone |
US4961890A (en) | 1986-08-08 | 1990-10-09 | Ethypharm | Method of preparing comtrolled release fenofibrate |
US4781183A (en) | 1986-08-27 | 1988-11-01 | American Cyanamid Company | Surgical prosthesis |
US4882168A (en) | 1986-09-05 | 1989-11-21 | American Cyanamid Company | Polyesters containing alkylene oxide blocks as drug delivery systems |
EP0258749B1 (en) | 1986-09-05 | 1992-06-17 | American Cyanamid Company | Surgical filament coating |
US4705820A (en) * | 1986-09-05 | 1987-11-10 | American Cyanamid Company | Surgical suture coating |
US4716203A (en) * | 1986-09-05 | 1987-12-29 | American Cyanamid Company | Diblock and triblock copolymers |
US4791929A (en) | 1986-09-23 | 1988-12-20 | American Cyanamid Company | Bioabsorbable coating for a surgical article |
US5147698A (en) | 1986-09-30 | 1992-09-15 | Minnesota Mining And Manufacturing Company | Pressure sensitive adhesive film article having high moisture vapor transmission rate |
US5009224A (en) | 1986-09-30 | 1991-04-23 | Minnesota Mining And Manufacturing Company | Method for attaching a pressure-sensitive film article having high moisture vapor transmission rate |
US4846165A (en) | 1986-11-26 | 1989-07-11 | Dentsply Research & Development Corp. | Wound dressing membrane |
US4960866A (en) | 1986-12-06 | 1990-10-02 | Boehringer Ingelheim Zentrale | Catalyst-free resorbable homopolymers and copolymers |
US5561157A (en) | 1986-12-23 | 1996-10-01 | Tristrata Inc | Method for enhancing the therapeutic effect of a composition comprising hydroquinone and comprising same |
US4965300A (en) | 1987-01-06 | 1990-10-23 | Bayer Aktiengesellschaft | Sequential copolymers based on cyclic carbonates and esters |
US4826945A (en) | 1987-06-09 | 1989-05-02 | Yissum Research Development Company | Biodegradable polymeric materials based on polyether glycols, processes for the preparation thereof and surgical articles made therefrom |
US5019100A (en) | 1987-07-01 | 1991-05-28 | Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno | Use of a polymer network, method for preparing a prepolymer and also preparation which yields a polymer network after curing |
US4804691A (en) | 1987-08-28 | 1989-02-14 | Richards Medical Company | Method for making a biodegradable adhesive for soft living tissue |
US4788879A (en) | 1987-09-17 | 1988-12-06 | Ulrich Dana L | Apparatus for hand operation of throttle and brake pedal, and methods of constructing and utilizing same |
US4891263A (en) | 1987-12-17 | 1990-01-02 | Allied-Signal Inc. | Polycarbonate random copolymer-based fiber compositions and method of melt-spinning same and device |
US5486593A (en) | 1987-12-17 | 1996-01-23 | United States Surgical Corporation | Medical devices fabricated from copolymers having recurring carbonate units |
US4920203A (en) | 1987-12-17 | 1990-04-24 | Allied-Signal Inc. | Medical devices fabricated from homopolymers and copolymers having recurring carbonate units |
US5412068A (en) | 1987-12-17 | 1995-05-02 | United States Surgical Corporation | Medical devices fabricated from homopolymers and copolymers having recurring carbonate units |
US5066772A (en) | 1987-12-17 | 1991-11-19 | Allied-Signal Inc. | Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides |
US5152781A (en) | 1987-12-17 | 1992-10-06 | Allied-Signal Inc. | Medical devices fabricated from homopolymers and copolymers having recurring carbonate units |
US5274074A (en) | 1987-12-17 | 1993-12-28 | United States Surgical Corporation | Medical devices fabricated from homopolymers and copolymers having recurring carbonate units |
US4916193A (en) | 1987-12-17 | 1990-04-10 | Allied-Signal Inc. | Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides |
US5256764A (en) | 1987-12-17 | 1993-10-26 | United States Surgical Corporation | Medical devices fabricated from homopolymers and copolymers having recurring carbonate units |
US5120802A (en) | 1987-12-17 | 1992-06-09 | Allied-Signal Inc. | Polycarbonate-based block copolymers and devices |
US5067961A (en) | 1988-02-18 | 1991-11-26 | Autogenesis Technologies, Inc. | Non-biodegradable two phase corneal implant and method for preparing same |
US5332802A (en) | 1988-02-18 | 1994-07-26 | Autogenesis Technologies, Inc. | Human collagen processing and autoimplant use |
US4900797A (en) | 1988-03-17 | 1990-02-13 | Bayer Aktiengesellschaft | Thermoplastic polycarbonate mixtures containing aliphatic |
US5264425A (en) | 1988-06-03 | 1993-11-23 | Italfarmaco S.P.A. | Glycosaminoglycan salts and pharmaceutical compositions containing them |
US4867602A (en) | 1988-06-17 | 1989-09-19 | Courtoise Robert L | Attachment for cleaning and refacing concrete joints |
US5296627A (en) | 1988-06-20 | 1994-03-22 | Ppg Industries, Inc. | Ethylenically unsaturated poly(alkyleneoxy) surfactants |
US5447966A (en) | 1988-07-19 | 1995-09-05 | United States Surgical Corporation | Treating bioabsorbable surgical articles by coating with glycerine, polalkyleneoxide block copolymer and gelatin |
US5051272A (en) | 1988-07-19 | 1991-09-24 | United States Surgical Corporation | Method for improving the storage stability of a polymeric article susceptible to hydrolytic degradation and resulting article |
US5502158A (en) | 1988-08-08 | 1996-03-26 | Ecopol, Llc | Degradable polymer composition |
US4938763A (en) | 1988-10-03 | 1990-07-03 | Dunn Richard L | Biodegradable in-situ forming implants and methods of producing the same |
US4938763B1 (en) | 1988-10-03 | 1995-07-04 | Atrix Lab Inc | Biodegradable in-situ forming implants and method of producing the same |
US5116929A (en) | 1988-10-14 | 1992-05-26 | Enichem Synthesis S.P.A. | Copolyester-diol polycarbonates, process for producing them and their use |
US5378801A (en) | 1988-11-01 | 1995-01-03 | Reichert; Dieter | Continuous process for the preparation of resorable polyesters and the use thereof |
US5137800A (en) | 1989-02-24 | 1992-08-11 | Stereographics Limited Partnership | Production of three dimensional bodies by photopolymerization |
US5100992A (en) | 1989-05-04 | 1992-03-31 | Biomedical Polymers International, Ltd. | Polyurethane-based polymeric materials and biomedical articles and pharmaceutical compositions utilizing the same |
US5043398A (en) | 1989-05-12 | 1991-08-27 | Hoechst Celanese Corporation | Grafting of functional compounds onto functional oxymethylene polymer backbones, with diisocyanate coupling agents, and the graft polymers thereof |
US5226877A (en) | 1989-06-23 | 1993-07-13 | Epstein Gordon H | Method and apparatus for preparing fibrinogen adhesive from whole blood |
US4997722A (en) | 1989-07-10 | 1991-03-05 | Edward Adler | Composition and method for improving adherence of copper foil to resinous substrates |
US5076807A (en) | 1989-07-31 | 1991-12-31 | Ethicon, Inc. | Random copolymers of p-dioxanone, lactide and/or glycolide as coating polymers for surgical filaments |
US5332475A (en) | 1989-08-02 | 1994-07-26 | University Of North Carolina At Chapel Hill | Cross-linking collagenous product |
US5081224A (en) | 1989-10-16 | 1992-01-14 | Kanegafuchi Chemical Industry Co., Ltd. | Process for production of olefin-terminated polyesters |
US5146945A (en) | 1989-12-06 | 1992-09-15 | Westinghouse Electric Corp. | Seal ring retainer and guide ring for valve plug |
US5201764A (en) | 1990-02-28 | 1993-04-13 | Autogenesis Technologies, Inc. | Biologically compatible collagenous reaction product and articles useful as medical implants produced therefrom |
US5480427A (en) | 1990-02-28 | 1996-01-02 | Darby & Darby | Biologically compatible collagenous reaction product and articles useful as medical implants produced therefrom |
US5104957A (en) | 1990-02-28 | 1992-04-14 | Autogenesis Technologies, Inc. | Biologically compatible collagenous reaction product and articles useful as medical implants produced therefrom |
US5019094A (en) | 1990-05-09 | 1991-05-28 | Ethicon, Inc. | Crystalline copolymers of p-dioxanone and poly(alkylene oxides) |
US5531707A (en) | 1990-06-08 | 1996-07-02 | Ab Astra | Device for introducing a substance into a body cavity of a patient |
US5540677A (en) | 1990-06-15 | 1996-07-30 | Rare Earth Medical, Inc. | Endoscopic systems for photoreactive suturing of biological materials |
US5360892A (en) | 1990-06-26 | 1994-11-01 | Arch Development Corporation | Water and UV degradable lactic acid polymers |
US5324307A (en) | 1990-07-06 | 1994-06-28 | American Cyanamid Company | Polymeric surgical staple |
US5252701A (en) | 1990-07-06 | 1993-10-12 | American Cyanamid Company | Segmented absorbable copolymer |
US5225129A (en) | 1990-07-19 | 1993-07-06 | Dsm N.V. | Method for the manufacture of polymer products from cyclic esters |
US5209776A (en) | 1990-07-27 | 1993-05-11 | The Trustees Of Columbia University In The City Of New York | Tissue bonding and sealing composition and method of using the same |
US5512091A (en) | 1990-08-13 | 1996-04-30 | Steiner; Carol A. | Associative polymer hydrogels |
US5410016A (en) | 1990-10-15 | 1995-04-25 | Board Of Regents, The University Of Texas System | Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers |
US5529914A (en) | 1990-10-15 | 1996-06-25 | The Board Of Regents The Univeristy Of Texas System | Gels for encapsulation of biological materials |
US5173301A (en) | 1990-11-27 | 1992-12-22 | Sanyo Chemical Industries, Ltd. | Surgical adhesive |
US5354336A (en) | 1991-01-29 | 1994-10-11 | Autogenesis Technologies, Inc. | Method for bonding soft tissue with collagen-based adhesives and sealants |
US5156613A (en) | 1991-02-13 | 1992-10-20 | Interface Biomedical Laboratories Corp. | Collagen welding rod material for use in tissue welding |
US5525646A (en) | 1991-03-04 | 1996-06-11 | Lundgren; Dan | Bioresorbable material and an article of manufacture made of such material for medical use |
US5308887A (en) | 1991-05-23 | 1994-05-03 | Minnesota Mining & Manufacturing Company | Pressure-sensitive adhesives |
US5463012A (en) | 1991-06-14 | 1995-10-31 | Mediolanum Farmaceutici S.P.A. | Polycarbonates and the use thereof for the preparation of bioerosible matrices |
US5425984A (en) | 1991-07-19 | 1995-06-20 | United States Surgical Corporation | Bioabsorbable melt spun fiber based on glycolide-containing copolymer |
US5567435A (en) | 1992-02-28 | 1996-10-22 | Board Of Regents, The University Of Texas System | Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers |
US5621050A (en) | 1992-03-02 | 1997-04-15 | American Cyanamid Company | Coating for tissue drag reduction |
US5476516A (en) | 1992-03-13 | 1995-12-19 | Albert Einstein College Of Medicine Of Yeshiva University | Anticalcification treatment for aldehyde-tanned biological tissue |
US5372585A (en) | 1992-04-09 | 1994-12-13 | Tiefenbrun; Jonathan | Instrument and associated method for applying biologically effective composition during laparoscopic operation |
US5573934A (en) | 1992-04-20 | 1996-11-12 | Board Of Regents, The University Of Texas System | Gels for encapsulation of biological materials |
US5589563A (en) | 1992-04-24 | 1996-12-31 | The Polymer Technology Group | Surface-modifying endgroups for biomedical polymers |
US5366756A (en) | 1992-06-15 | 1994-11-22 | United States Surgical Corporation | Method for treating bioabsorbable implant material |
US5385606A (en) | 1992-07-06 | 1995-01-31 | Kowanko; Nicholas | Adhesive composition and method |
US5516825A (en) | 1992-08-13 | 1996-05-14 | Zeneca Limited | Biodegradable polymer compositions |
US5631336A (en) | 1992-08-27 | 1997-05-20 | Consiglio Nazionale Delle Ricerche | Chain-terminated N-vinyl lactam polymers and graft-copolymers and methods for making same |
US5665474A (en) | 1992-10-02 | 1997-09-09 | Cargill, Incorporated | Paper having a melt-stable lactide polymer coating and process for manufacture thereof |
US5278200A (en) | 1992-10-30 | 1994-01-11 | Medtronic, Inc. | Thromboresistant material and articles |
US5397816A (en) | 1992-11-17 | 1995-03-14 | Ethicon, Inc. | Reinforced absorbable polymers |
US5521280A (en) | 1992-11-17 | 1996-05-28 | Ethicon, Inc. | Reinforced absorbable polymers |
US5468253A (en) | 1993-01-21 | 1995-11-21 | Ethicon, Inc. | Elastomeric medical device |
US5449743A (en) | 1993-01-29 | 1995-09-12 | Shiro Kobayashi | Method for ring opening polymerization using a hydrolase catalyst |
US5459177A (en) | 1993-03-09 | 1995-10-17 | Sun Medical Co., Ltd. | Adhesive for soft tissue and kit thereof |
US5552452A (en) | 1993-03-15 | 1996-09-03 | Arch Development Corp. | Organic tissue glue for closure of wounds |
US5310599A (en) | 1993-05-06 | 1994-05-10 | E. I. Du Pont De Nemours And Company | Method for making polymers of alpha-hydroxy acids |
US5412067A (en) | 1993-05-10 | 1995-05-02 | Mitsui Toatsu Chemicals, Inc. | Preparation process of polyester |
US5522841A (en) | 1993-05-27 | 1996-06-04 | United States Surgical Corporation | Absorbable block copolymers and surgical articles fabricated therefrom |
US5403347A (en) | 1993-05-27 | 1995-04-04 | United States Surgical Corporation | Absorbable block copolymers and surgical articles fabricated therefrom |
US5403826A (en) | 1993-05-28 | 1995-04-04 | Abbott Laboratories | Nutritional product for persons infected with human immunodeficiency virus |
US5554665A (en) | 1993-06-23 | 1996-09-10 | Dentsply Research & Development Corp. | Method and dispenser for making dental products |
US5496872A (en) | 1993-07-21 | 1996-03-05 | Imedex | Adhesive compositions for surgical use |
US5359026A (en) | 1993-07-30 | 1994-10-25 | Cargill, Incorporated | Poly(lactide) copolymer and process for manufacture thereof |
US5594095A (en) | 1993-07-30 | 1997-01-14 | Cargill, Incorporated | Viscosity-modified lactide polymer composition and process for manufacture thereof |
US5530038A (en) | 1993-08-02 | 1996-06-25 | Sun Medical Co., Ltd. | Primer composition and curable composition |
US5563238A (en) | 1993-08-05 | 1996-10-08 | Arch Development Corporation | Water and UV degradable lactic acid polymers |
US5508317A (en) | 1993-08-06 | 1996-04-16 | Ciba-Geigy Corporation | Photocrosslinked polymers |
US5531709A (en) | 1993-09-23 | 1996-07-02 | Heraeus Kulzer Gmbh | Syringe for the controlled discharge of viscous materials |
US5698661A (en) | 1993-11-05 | 1997-12-16 | Asta Medica Aktiengesellschaft | High molecular weight polyesterpolycarbonates and the use thereof for the preparation of bioerosible matrices |
US5391707A (en) | 1993-12-10 | 1995-02-21 | United States Surgical Corporation | Process for the production of dioxanone |
US5484913A (en) | 1993-12-23 | 1996-01-16 | Johnson & Johnson Medical, Inc. | Calcium-modified oxidized cellulose hemostat |
US5550209A (en) | 1994-03-04 | 1996-08-27 | Daicel Chemical Industries, Ltd. | Monodispersed polymer or copolymer and a preparation process thereof |
US5629384A (en) | 1994-05-17 | 1997-05-13 | Consiglio Nazionale Delle Ricerche | Polymers of N-acryloylmorpholine activated at one end and conjugates with bioactive materials and surfaces |
US5631322A (en) | 1994-05-17 | 1997-05-20 | Consiglio Nazionale Delle Ricerche | Polymers of N-acryloylmorpholine activated at one end and conjugates with bioactive materials and surfaces |
US5621119A (en) | 1994-07-22 | 1997-04-15 | Heraeus Kulzer Gmbh & Co., Kg | Di(meth)acrylates having cyclic carbonate groups |
US5525647A (en) | 1994-08-01 | 1996-06-11 | American Dental Association Health Foundation | Method and device for controllably affecting the reaction of dental adhesives |
US5478921A (en) | 1994-08-25 | 1995-12-26 | United States Surgical Corporation | Method of purifying bioabsorable polymer |
US5650234A (en) | 1994-09-09 | 1997-07-22 | Surface Engineering Technologies, Division Of Innerdyne, Inc. | Electrophilic polyethylene oxides for the modification of polysaccharides, polypeptides (proteins) and surfaces |
US5607686A (en) | 1994-11-22 | 1997-03-04 | United States Surgical Corporation | Polymeric composition |
US5698213A (en) | 1995-03-06 | 1997-12-16 | Ethicon, Inc. | Hydrogels of absorbable polyoxaesters |
US5527864A (en) | 1995-08-08 | 1996-06-18 | Suggs; Laura J. | Poly(propylene fumarate-co-ethylene oxide) |
US5665428A (en) | 1995-10-25 | 1997-09-09 | Macromed, Inc. | Preparation of peptide containing biodegradable microspheres by melt process |
US5633342A (en) | 1995-10-27 | 1997-05-27 | Chronopol, Inc. | Method for the synthesis of environmentally degradable block copolymers |
US5658995A (en) | 1995-11-27 | 1997-08-19 | Rutgers, The State University | Copolymers of tyrosine-based polycarbonate and poly(alkylene oxide) |
Non-Patent Citations (78)
Title |
---|
ACS Meeting Briefs, "Carbonate Copolymers: New branch of epoxybutene tree," C& EN p. 59 (1997). |
ACS Meeting Briefs, Carbonate Copolymers: New branch of epoxybutene tree, C & EN p. 59 (1997). * |
Aida, et al., "Alternating Copolymerization of Carbon Dioxide and Epoxide Catalyzed by the Aluminum Porphyrin-Quaternary Organic Salt or--Triphenylphosphine System. Synthesis of Polycarbonate with Well-Controlled Molecular Weight," Macromolecules 19:8-13 (1986). |
Aida, et al., Alternating Copolymerization of Carbon Dioxide and Epoxide Catalyzed by the Aluminum Porphyrin Quaternary Organic Salt or Triphenylphosphine System. Synthesis of Polycarbonate with Well Controlled Molecular Weight, Macromolecules 19:8 13 (1986). * |
Bailey, et al., "Synthesis of Poly-ε-Caproictone via a Free Radical Mechanism, Free Radical Ring-Opening Polymerization of 2-Methylene-1,3-Dioxepane," Journal of Polymer Science 20:3021-3030 (1982). |
Bailey, et al., Synthesis of Poly Caproictone via a Free Radical Mechanism, Free Radical Ring Opening Polymerization of 2 Methylene 1,3 Dioxepane, Journal of Polymer Science 20:3021 3030 (1982). * |
Barrows, "Degradable implant materials: A review of synthetic absorbable polymers and their applicatios," Clinical Materials 1:233-257 (1986). |
Barrows, Degradable implant materials: A review of synthetic absorbable polymers and their applicatios, Clinical Materials 1:233 257 (1986). * |
Chen, et al., "Novel Graft Copolymers of a Temperature-Sensitive Polymer Grafted to a pH-Sensitive, Bioadhesive Polymer for Controlled Drug Delivery," 21st Annual Meeting of the Society of Biomaterials (1995). |
Chen, et al., Novel Graft Copolymers of a Temperature Sensitive Polymer Grafted to a pH Sensitive, Bioadhesive Polymer for Controlled Drug Delivery, 21st Annual Meeting of the Society of Biomaterials (1995). * |
CIMA, et al., "Hepatocyte Responses to PEO-Tethered Carbohydrates Depend on Tether Conformation," 21st Annual Meeting of the Society of Biomaterials 147 (1995). |
CIMA, et al., Hepatocyte Responses to PEO Tethered Carbohydrates Depend on Tether Conformation, 21st Annual Meeting of the Society of Biomaterials 147 (1995). * |
Constancis, et al., Colcys as Surgical Adhesives, Ex Vivo Characterization of Mechanical and Adhesive Properties, 21st Annual Meeting of the Society of Biomaterials 258 (1995). * |
Dumanian, et al., "A New Photopolymerizable Blood Vessel Glue that Seals Human Vessel Anastomoses Without Augmenting Thrombogenicity," Plastic and Reconstructive Surgery 95(5):901-907 (1995). |
Dumanian, et al., A New Photopolymerizable Blood Vessel Glue that Seals Human Vessel Anastomoses Without Augmenting Thrombogenicity, Plastic and Reconstructive Surgery 95(5):901 907 (1995). * |
Dupont, et al., Collagen Gel Sealant (Glue) Based On Controlled Oxidized Collagen Ex Vivo and In Vivo Characterization, 21st Annual Meeting of the Society of Biomaterials 242 (1995). * |
Frenkel, et al., A Collagen Bilayer Implant for Articular Cartilage Repair in a Rabbit Model, 21st Annual Meeting of the Society of Biomaterials 305 (1995). * |
Gagnieu, et al., "Colcys: New Crosslinkable Atelocollagens Synthesis and physico-chemical properties of highly grafted polymers," 21st Annual Meeting of the Society of Biomaterials 256 (1995). |
Gagnieu, et al., Colcys: New Crosslinkable Atelocollagens Synthesis and physico chemical properties of highly grafted polymers, 21st Annual Meeting of the Society of Biomaterials 256 (1995). * |
Gershkovich, et al., "Post-Surgical Adhesion Prevention with Bioresorbable Gels of Amine Modified Hyaluronic Acid," 21st Meeting of the Society of Biomaterials 66 (1995). |
Gershkovich, et al., Post Surgical Adhesion Prevention with Bioresorbable Gels of Amine Modified Hyaluronic Acid, 21st Meeting of the Society of Biomaterials 66 (1995). * |
Hata, et al., "Enzymatic Polymerization of 2-Hydroxyethylmethacrylate for Artificial Embolization," The Third Word Biomaterials Congress 301 (1988). |
Hata, et al., Enzymatic Polymerization of 2 Hydroxyethylmethacrylate for Artificial Embolization, The Third Word Biomaterials Congress 301 (1988). * |
Herbert, et al., "Polytetramethylene Oxide Blended With Polyurethane Reduces Platelet Adhesion", 21st Annual Meeting of the Society of Biomaterials 271 (1995). |
Herbert, et al., Polytetramethylene Oxide Blended With Polyurethane Reduces Platelet Adhesion , 21st Annual Meeting of the Society of Biomaterials 271 (1995). * |
Hsu, et al., "Study On Aqueous Polymerizations Of Vinyl Monomers Initiated By Metal Oxidant-Chelating Agent Redox Initiators", J. Polymer Science: Part A: Polymer Chem. 31:3213-3222 (1993). |
Hsu, et al., Study On Aqueous Polymerizations Of Vinyl Monomers Initiated By Metal Oxidant Chelating Agent Redox Initiators , J. Polymer Science: Part A: Polymer Chem. 31:3213 3222 (1993). * |
Inoue, "Copolymerization of Carbon Dioxide and Epoxide: Functionality of the Copolymer," J. Macromol. Sci. Chem. A13(5):651-664 (1979). |
Inoue, "Copolymerization of Carbon Dioxide," Department of Synthetic Chemistry, Faculty of Engineering, University of Tokyo, 1-42 (1974). |
Inoue, Copolymerization of Carbon Dioxide and Epoxide: Functionality of the Copolymer, J. Macromol. Sci. Chem. A13(5):651 664 (1979). * |
Inoue, Copolymerization of Carbon Dioxide, Department of Synthetic Chemistry, Faculty of Engineering, University of Tokyo, 1 42 (1974). * |
Inoue, et al., "Synthesis and Thermal Degradation of Carbon Dioxide-Epoxide Copolymer," Applied Polymer Symposium 26:257-267 (1975). |
Inoue, et al., Synthesis and Thermal Degradation of Carbon Dioxide Epoxide Copolymer, Applied Polymer Symposium 26:257 267 (1975). * |
Kawaguchi, et al., "Examination of Biodegradability of Poly(ethylene carbonate) and Poly(propylene carbonate) in the Peritoneal Cavity in Rats," Chem. Pharm. Bull. 31(4:1400-1403 (1983). |
Kawaguchi, et al., "Release Profiles of 5-Fluorouracil and Its Derivative from Polycarbonate Matrices in Vitro," Chem. Pharm. Bull. 30(4):1517-1520 (1982). |
Kawaguchi, et al., Examination of Biodegradability of Poly(ethylene carbonate) and Poly(propylene carbonate) in the Peritoneal Cavity in Rats, Chem. Pharm. Bull. 31(4:1400 1403 (1983). * |
Kawaguchi, et al., Release Profiles of 5 Fluorouracil and Its Derivative from Polycarbonate Matrices in Vitro, Chem. Pharm. Bull. 30(4):1517 1520 (1982). * |
Keul, et al., "Anionic ring-opening polymerization of 2,2-dimethyltrimethylene carbonate," Makromol. Chem. 187:2579-2589 (1986). |
Keul, et al., Anionic ring opening polymerization of 2,2 dimethyltrimethylene carbonate, Makromol. Chem. 187:2579 2589 (1986). * |
Kobayashi, et al., "Water-curable and Biodegradable prepolymers," Journal of Biomedical Materials Research 25:1481-1494 (1991). |
Kobayashi, et al., Water curable and Biodegradable prepolymers, Journal of Biomedical Materials Research 25:1481 1494 (1991). * |
Kojima, et al., "Preparation and Evaluation in Vitro of Polycarbonate Microspheres Containing Local Anesthetics," Chem. Pharm. Bull. 32(7):2795-2802 (1984). |
Kojima, et al., Preparation and Evaluation in Vitro of Polycarbonate Microspheres Containing Local Anesthetics, Chem. Pharm. Bull. 32(7):2795 2802 (1984). * |
Kricheldorf, et al., "Polylactones. 16. Cationic Polymerization of Trimethylene Carbonate and Other Cyclic Carbonates," J. Macromol. Sci.--Chem. A26(4):631-644 (1989). |
Kricheldorf, et al., "Polymers of Carbonic Acid, 12--Spontaneous and Hematin-Initiated Polymerizations of Trimethylene Carbonate and Neopentylene Carbonate," Macromol. Chem. Phys. 197:1043-1054 (1996). |
Kricheldorf, et al., Polylactones. 16. Cationic Polymerization of Trimethylene Carbonate and Other Cyclic Carbonates, J. Macromol. Sci. Chem. A26(4):631 644 (1989). * |
Kricheldorf, et al., Polymers of Carbonic Acid, 12 Spontaneous and Hematin Initiated Polymerizations of Trimethylene Carbonate and Neopentylene Carbonate, Macromol. Chem. Phys. 197:1043 1054 (1996). * |
M u ller, et al., Lithium and Potassium Alcoholates of Poly(ethylene glycol)s as Initiators for the Anionic Polymerization of 2,2 Dimethyltrimethylene Carbonate. Synthesis of AB and ABA Block Copolymers, Euro. Polym. J. 27(12):1323 1330 (1991). * |
McPherson, et al., Scaling Analysis of the Prevention of Protein Adsorption by Grafted PEO Chains, 21st Annual Meeting of the Society of Biomaterials 224 (1995). * |
Miller, et al., "Prevention of Post-Surgical Tendon Adhesions Using Hyaluronic Acid Systems," 21st Annual Meeting of Society of Biomaterials 382 (1995). |
Miller, et al., Prevention of Post Surgical Tendon Adhesions Using Hyaluronic Acid Systems, 21st Annual Meeting of Society of Biomaterials 382 (1995). * |
Moore, et al., An Injectable Biodegradable Drug Delivery System Based on Acrylic Terminated Poly( Caprolactone), 21st Annual Meeting of the Society of Biomaterials 186 (1995). * |
Moore, et al., An Injectable Biodegradable Drug Delivery System Based on Acrylic Terminated Poly(ε-Caprolactone), 21st Annual Meeting of the Society of Biomaterials 186 (1995). |
Mouritzen, et al., "The effect of fibrin glueing to seal bronchial and alveolar leakages after pulmonary resections decortications," Eur. J. Cardio-thorac Surg. 7(2):75-80 (1993). |
Mouritzen, et al., The effect of fibrin glueing to seal bronchial and alveolar leakages after pulmonary resections decortications, Eur. J. Cardio thorac Surg. 7(2):75 80 (1993). * |
Muller, et al., "Lithium and Potassium Alcoholates of Poly(ethylene-glycol)s as Initiators for the Anionic Polymerization of 2,2-Dimethyltrimethylene Carbonate. Synthesis of AB and ABA Block Copolymers," Euro. Polym. J. 27(12):1323-1330 (1991). |
Pemberton, et al., "Polymerization of vinyl acetate using visible radiation and a dye-reducing agent sensitizer: 1. Pre-initiation and initiation reactions involving ethyl eosin and ascorbic acid," Polymer 25:536-542 (1984). |
Pemberton, et al., "Polymerization of vinyl acetate using visible radiation and a dye-reducing agent sensitizer: 2. Kinetic studies and polymerization mechanism," Polymer 25:543-549 (1984). |
Pemberton, et al., Polymerization of vinyl acetate using visible radiation and a dye reducing agent sensitizer: 1. Pre initiation and initiation reactions involving ethyl eosin and ascorbic acid, Polymer 25:536 542 (1984). * |
Pemberton, et al., Polymerization of vinyl acetate using visible radiation and a dye reducing agent sensitizer: 2. Kinetic studies and polymerization mechanism, Polymer 25:543 549 (1984). * |
Reed, In Vivo and In Vitro Studies of Biodegradable Polymers for Use in Medicine, Thesis submitted in accordance with the requirements of the University of Liverpool for the degree of Doctor of Philosophy (Jul., 1978). * |
Rimpler, "Gluing--a challenge in surgery," Int. J. Adhesion and Adhesives 16:17-20 (1996). |
Rimpler, Gluing a challenge in surgery, Int. J. Adhesion and Adhesives 16:17 20 (1996). * |
Roby, et al., Absorbable Sutures Based on Glycolide/Trimethylene Carbonate Copolymers, 21st Annual Meeting of the Society of Biomaterials 216 (1985). * |
Sawhney, et al., "Optimization of photopolymerized bioerodible hydrogel properties for adhesion prevention," Journal of Biomedical Materials Research 28(7):831-838 (1994). |
Sawhney, et al., Optimization of photopolymerized bioerodible hydrogel properties for adhesion prevention, Journal of Biomedical Materials Research 28(7):831 838 (1994). * |
Sierra, et al., "Skullbase Cerebrospinal Fluid Leakage Control With a Fibrin-based Composite Tissue Adhesive," 21st Annual Meeting of the Society of Biomaterials 247 (1995). |
Sierra, et al., Skullbase Cerebrospinal Fluid Leakage Control With a Fibrin based Composite Tissue Adhesive, 21st Annual Meeting of the Society of Biomaterials 247 (1995). * |
Takanashi, et al., "Functional Polycarbonate by Copolymerization of Carbon Dioxide and Epoxide: Synthesis and Hydrolysis," Makromol. Chem. 183:2085-2092 (1982). |
Takanashi, et al., Functional Polycarbonate by Copolymerization of Carbon Dioxide and Epoxide: Synthesis and Hydrolysis, Makromol. Chem. 183:2085 2092 (1982). * |
Tardy, et al., "New Surgical Sealant (Glue) Based on Controlled Oxidized Collage--Design and Physico-Chemical Characterization," 21st Annual Meeting of the Society of Biomaterials 254 (1995). |
Tardy, et al., New Surgical Sealant (Glue) Based on Controlled Oxidized Collage Design and Physico Chemical Characterization, 21st Annual Meeting of the Society of Biomaterials 254 (1995). * |
Tiollier, et al., "Colcys as Surgical Adhesives--In Vivo Characterization and Biocompatability," 21st Annual Meeting of the Society of Biomaterials (1995). |
Tiollier, et al., Colcys as Surgical Adhesives In Vivo Characterization and Biocompatability, 21st Annual Meeting of the Society of Biomaterials (1995). * |
Tiollier, et al., Novel Development of Collagen/Gelatin Surgical Adhesives for Surgical Soft Tissue Applications, 21st Annual Meeting of the Society of Biomaterials 257 (1995). * |
Tomizawa, et al., "Polyepoxy Compound Cross-Linked Cotton Type Collagen Hemostat," 21st Annual Meeting of the Society of Biomatrials 273 (1995). |
Tomizawa, et al., Polyepoxy Compound Cross Linked Cotton Type Collagen Hemostat, 21st Annual Meeting of the Society of Biomatrials 273 (1995). * |
Truong, et al., In Vitro Conditions for Accelerated Hydrolysis of Bioabsorbable Fibers, 21st Annual Meeting of the Society of Biomaterials 436 (1995). * |
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US20090209658A1 (en) * | 2000-03-13 | 2009-08-20 | Goupil Dennis W | Embolic compositions |
USRE48302E1 (en) | 2000-03-13 | 2020-11-10 | Biocure, Inc. | Embolic compositions |
USRE47121E1 (en) | 2000-03-13 | 2018-11-13 | Biocure, Inc. | Embolic compositions |
US7070809B2 (en) | 2000-03-13 | 2006-07-04 | Biocure, Inc. | Hydrogel biomedical articles |
US8221735B2 (en) | 2000-03-13 | 2012-07-17 | Biocure, Inc. | Embolic compositions |
USRE47873E1 (en) | 2000-03-13 | 2020-02-25 | Biocompatibles Uk Limited | Embolic compositions |
US6652883B2 (en) | 2000-03-13 | 2003-11-25 | Biocure, Inc. | Tissue bulking and coating compositions |
US20030211073A1 (en) * | 2000-03-13 | 2003-11-13 | Goupil Dennis W. | Tissue bulking and coating compositions |
US20010056301A1 (en) * | 2000-03-13 | 2001-12-27 | Goupil Dennis W. | Hydrogel biomedical articles |
US20030104347A1 (en) * | 2000-03-21 | 2003-06-05 | Yuichi Mori | Coating material for living organism tissue, coated product from living organism tissue and method of coating living organism material |
US6673385B1 (en) * | 2000-05-31 | 2004-01-06 | Advanced Cardiovascular Systems, Inc. | Methods for polymeric coatings stents |
US7682648B1 (en) | 2000-05-31 | 2010-03-23 | Advanced Cardiovascular Systems, Inc. | Methods for forming polymeric coatings on stents |
US20040077780A1 (en) * | 2000-09-28 | 2004-04-22 | Battelle Memorial Institute | Thermogelling oligopeptide polymers |
US6841617B2 (en) | 2000-09-28 | 2005-01-11 | Battelle Memorial Institute | Thermogelling biodegradable aqueous polymer solution |
US7087244B2 (en) | 2000-09-28 | 2006-08-08 | Battelle Memorial Institute | Thermogelling oligopeptide polymers |
US20020173586A1 (en) * | 2000-09-28 | 2002-11-21 | Jeong Byeong Moon | Thermogelling biodegradable aqueous polymer solution |
KR100451910B1 (en) * | 2000-10-05 | 2004-10-08 | 주식회사 바이오폴리테크 | A water soluble and biodegradable polymer gel, and a process of preparing for the same |
US6713593B2 (en) * | 2000-10-11 | 2004-03-30 | Pohang Iron & Steel Co., Ltd. | Copolymer comprising alkylene carbonate and method of preparing same |
US7074424B2 (en) * | 2000-11-28 | 2006-07-11 | Genzyme Corporation | Polyalkylene glycol viscosity-enhancing polymeric formulations |
US20020127196A1 (en) * | 2000-11-28 | 2002-09-12 | Focal, Inc. | Polyalkylene glycol viscosity-enhancing polymeric formulations |
US7022343B2 (en) | 2000-12-27 | 2006-04-04 | Genzyme Corporation | Controlled release of anti-arrhythmic agents |
US20020187182A1 (en) * | 2001-02-14 | 2002-12-12 | Genzyme Corporation | Biocompatible fleece for hemostasis and tissue engineering |
US7763769B2 (en) | 2001-02-16 | 2010-07-27 | Kci Licensing, Inc. | Biocompatible wound dressing |
US7700819B2 (en) | 2001-02-16 | 2010-04-20 | Kci Licensing, Inc. | Biocompatible wound dressing |
US8163974B2 (en) | 2001-02-16 | 2012-04-24 | Kci Licensing, Inc. | Biocompatible wound dressing |
US8735644B2 (en) | 2001-02-16 | 2014-05-27 | Kci Licensing, Inc. | Biocompatible wound dressing |
US8084664B2 (en) | 2001-02-16 | 2011-12-27 | Kci Licensing, Inc. | Biocompatible wound dressing |
WO2003047462A1 (en) * | 2001-03-12 | 2003-06-12 | Clemson University | Polysaccharide-based polmerizable hydrogels |
US20040185086A1 (en) * | 2001-03-12 | 2004-09-23 | Stephen Massia | Polysaccharide-based polymerizable hydrogels |
US20050002893A1 (en) * | 2001-10-24 | 2005-01-06 | Helmut Goldmann | Composition consisting of a polymer containing amino groups and an aldehyde containing at least three aldehyde groups |
US9040060B2 (en) * | 2002-02-15 | 2015-05-26 | Nektar Therapeutics | Hydrolytically degradable alkylene oxide based polymers |
US20110217343A1 (en) * | 2002-02-15 | 2011-09-08 | Nektar Therapeutics | Hydrolytically degradable alkylene oxide based polymers |
US20060239961A1 (en) * | 2002-02-15 | 2006-10-26 | Nektar Therapeutics Al, Corporation | Hydrolytically degradable alkylene oxide based polymers |
US7972619B2 (en) | 2002-05-03 | 2011-07-05 | Biopsy Sciences, Llc | Biodegradable polymer for marking tissue and sealing tracts |
US20080161848A1 (en) * | 2002-05-03 | 2008-07-03 | Biopsy Sciences, Llc | Biodegradable polymer for making tissue and sealing tracts |
US20040091462A1 (en) * | 2002-08-20 | 2004-05-13 | Lin Steve T. | Composition for the carrying and delivery of bone growth inducing material and methods for producing and applying the composition |
US20070155926A1 (en) * | 2003-03-28 | 2007-07-05 | Krzysztof Matyjaszewski | Degradable polymers |
US7776351B2 (en) | 2003-05-13 | 2010-08-17 | Medtronic, Inc. | Moisture curable materials for delivery of agents, methods, and medical devices |
US20040228902A1 (en) * | 2003-05-13 | 2004-11-18 | Medtronic, Inc. | Moisture curable materials for delivery of agents, methods, and medical devices |
US20050004324A1 (en) * | 2003-05-21 | 2005-01-06 | Ward Robert S. | Permselective structurally robust membrane material |
US20060183871A1 (en) * | 2003-05-21 | 2006-08-17 | Ward Robert S | Biosensor membrane material |
US7157528B2 (en) | 2003-05-21 | 2007-01-02 | The Polymer Technology Group | Permselective structurally robust membrane material |
US7687586B2 (en) | 2003-05-21 | 2010-03-30 | Isense Corporation | Biosensor membrane material |
US20080267901A1 (en) * | 2003-07-03 | 2008-10-30 | Dirk Wybe Grijpma | Biocompatible Polymer Networks |
WO2005002596A1 (en) * | 2003-07-03 | 2005-01-13 | Universiteit Twente | Biocompatible polymer networks |
US20120308481A1 (en) * | 2003-08-11 | 2012-12-06 | Pathak Holdings Llc | Radio-opaque compounds, compositions containing same and methods of their synthesis and use |
US9186422B2 (en) * | 2003-08-11 | 2015-11-17 | Pathak Holdings Llc | Radio-opaque compounds, compositions containing same and methods of their synthesis and use |
CN100497437C (en) * | 2003-11-17 | 2009-06-10 | 中国科学院过程工程研究所 | Preparation method of polyethylene carboxylic acid and its use |
US20050178395A1 (en) * | 2003-11-20 | 2005-08-18 | Angiotech International Ag | Polymer compositions and methods for their use |
US20070276101A1 (en) * | 2004-03-05 | 2007-11-29 | Carnegie Mellon Uiniversity | Atom Transfer Radical Polymerization Process |
US8404788B2 (en) | 2004-03-05 | 2013-03-26 | Carnegie Mellon University | Atom transfer radical polymerization process |
US7893174B2 (en) | 2004-03-05 | 2011-02-22 | Carnegie Mellon University | Atom transfer radical polymerization process |
US20110218306A1 (en) * | 2004-03-05 | 2011-09-08 | Carnegie Mellon University | Atom transfer radical polymerization process |
US20050234121A1 (en) * | 2004-03-24 | 2005-10-20 | Binder Thomas P | Vegetable based dioxanone derivatives, synthesis and uses thereof |
US7754823B2 (en) | 2004-03-24 | 2010-07-13 | Archer-Daniels-Midland Company | Vegetable based dioxanone derivatives, synthesis and uses thereof |
US8460695B2 (en) | 2004-04-20 | 2013-06-11 | Genzyme Corporation | Making a soft tissue prosthesis for repairing a defect of an abdominal wall or a pelvic cavity wall |
US20050244455A1 (en) * | 2004-04-20 | 2005-11-03 | Greenawalt Keith E | Surgical prosthesis |
WO2005105172A1 (en) | 2004-04-20 | 2005-11-10 | Genzyme Corporation | Surgical mesh-like implant |
US8323675B2 (en) * | 2004-04-20 | 2012-12-04 | Genzyme Corporation | Soft tissue prosthesis for repairing a defect of an abdominal wall or a pelvic cavity wall |
US20050281866A1 (en) * | 2004-05-24 | 2005-12-22 | Genzyme Corporation | Adherent polymeric compositions |
US20050271727A1 (en) * | 2004-06-07 | 2005-12-08 | Callisyn Pharmaceuticals, Inc. | Biodegradable and biocompatible crosslinked polymer hydrogel prepared from PVA and/or PEG macromer mixtures |
US7666225B2 (en) | 2004-06-29 | 2010-02-23 | Hassan Chaouk | Spinal disc nucleus pulposus implant |
US20050288789A1 (en) * | 2004-06-29 | 2005-12-29 | Hassan Chaouk | Spinal disc nucleus pulposus implant |
US20050287218A1 (en) * | 2004-06-29 | 2005-12-29 | Hassan Chaouk | Biomaterial |
US20070161753A1 (en) * | 2004-08-02 | 2007-07-12 | Min-Hyo Seo | Biodegradable multi-block polymeric composition capable of sol-gel trainsition and pharmaceutical composition comprising the same |
WO2006014067A1 (en) | 2004-08-02 | 2006-02-09 | Samyang Corporation | Biodegradable multi-block polymeric composition capable of sol-gel transition |
US7655735B2 (en) | 2004-08-02 | 2010-02-02 | Samyang Corporation | Biodegradable multi-block polymeric composition capable of sol-gel transition and pharmaceutical composition comprising the same |
US20090030451A1 (en) * | 2005-02-09 | 2009-01-29 | Hadba Ahmad R | Synthetic Sealants |
US9707252B2 (en) | 2005-02-09 | 2017-07-18 | Covidien Lp | Synthetic sealants |
EP1904553A4 (en) * | 2005-07-06 | 2013-04-24 | Molly S Shoichet | Method of biomolecule immobilization on polymers using click-type chemistry |
US9290617B2 (en) | 2005-07-06 | 2016-03-22 | Molly S. Shoichet | Method of biomolecule immobilization on polymers using click-type chemistry |
US20090297609A1 (en) * | 2005-07-06 | 2009-12-03 | Shoichet Molly S | Method of Biomolecule Immobilization On Polymers Using Click-Type Chemistry |
EP1904553A1 (en) * | 2005-07-06 | 2008-04-02 | Molly S. Shoichet | Method of biomolecule immobilization on polymers using click-type chemistry |
US8273823B2 (en) | 2005-08-23 | 2012-09-25 | Carnegie Mellon University | Atom transfer radical polymerization in microemulsion and true emulsion polymerization processes |
US7893173B2 (en) | 2005-08-26 | 2011-02-22 | Carnegie Mellon University | Polymerization process with catalyst reactivation |
US20090312505A1 (en) * | 2005-08-26 | 2009-12-17 | Krzysztof Matyjaszewski | Polymerization Process with catalyst reactivation |
US20110065875A1 (en) * | 2005-08-26 | 2011-03-17 | Krzysztof Matyjaszewski | Polymerization process with catalyst reactivation |
US8512736B2 (en) * | 2005-09-21 | 2013-08-20 | Surmodics, Inc. | Coatings including natural biodegradable polysaccharides and uses thereof |
US20070065481A1 (en) * | 2005-09-21 | 2007-03-22 | Chudzik Stephen J | Coatings including natural biodegradable polysaccharides and uses thereof |
US20070112115A1 (en) * | 2005-11-15 | 2007-05-17 | Shalaby Shalaby W | Inorganic-organic hybrid micro-/nanofibers |
US20070149641A1 (en) * | 2005-12-28 | 2007-06-28 | Goupil Dennis W | Injectable bone cement |
WO2007121055A1 (en) * | 2006-04-11 | 2007-10-25 | Medtronic Vascular, Inc. | Biodegradable biocompatible amphiphilic copolymers for coating and manufacturing medical devices |
US20070237803A1 (en) * | 2006-04-11 | 2007-10-11 | Medtronic Vascular, Inc. | Biodegradable Biocompatible Amphiphilic Copolymers for Coating and Manufacturing Medical Devices |
US20100143286A1 (en) * | 2006-10-09 | 2010-06-10 | Carnegie Mellon University | Preparation of functional gel particles with a dual crosslink network |
US8367051B2 (en) | 2006-10-09 | 2013-02-05 | Carnegie Mellon University | Preparation of functional gel particles with a dual crosslink network |
US8722039B2 (en) | 2006-12-15 | 2014-05-13 | Lifebond Ltd. | Gelatin-transglutaminase hemostatic dressings and sealants |
US9636433B2 (en) | 2006-12-15 | 2017-05-02 | Lifebond Ltd | Gelatin-transglutaminase hemostatic dressings and sealants |
US9017664B2 (en) | 2006-12-15 | 2015-04-28 | Lifebond Ltd. | Gelatin-transglutaminase hemostatic dressings and sealants |
US9655988B2 (en) | 2006-12-15 | 2017-05-23 | Lifebond Ltd | Gelatin-transglutaminase hemostatic dressings and sealants |
US8133484B2 (en) | 2006-12-15 | 2012-03-13 | Lifebond Ltd | Hemostatic materials and dressing |
US20100249271A1 (en) * | 2007-05-23 | 2010-09-30 | Carnegie Mellon University | Hybrid partice composite structures with reduced scattering |
US8252880B2 (en) | 2007-05-23 | 2012-08-28 | Carnegie Mellon University | Atom transfer dispersion polymerization |
US8865797B2 (en) | 2007-05-23 | 2014-10-21 | Carnegie Mellon University | Hybrid particle composite structures with reduced scattering |
US10251954B2 (en) | 2007-07-09 | 2019-04-09 | Incept, Llc | Hydrogel polymeric compositions and methods |
US11324828B2 (en) | 2007-07-09 | 2022-05-10 | Incept, Llc | Hydrogel polymeric compositions and methods |
US9370485B2 (en) | 2007-07-09 | 2016-06-21 | Incept, Llc | Hydrogel polymeric compositions and methods |
US9125807B2 (en) | 2007-07-09 | 2015-09-08 | Incept Llc | Adhesive hydrogels for ophthalmic drug delivery |
US9775906B2 (en) | 2007-07-09 | 2017-10-03 | Incept Llc | Hydrogel polymeric compositions and methods |
KR100927533B1 (en) * | 2007-10-23 | 2009-11-17 | 한남대학교 산학협력단 | Polyhydroxyethyl aspartamide-polyparadioxanone copolymer and preparation method thereof |
EP2217251A1 (en) * | 2007-11-02 | 2010-08-18 | Genzyme Corporation | Methods of augmenting or repairing soft tissue |
EP2217251A4 (en) * | 2007-11-02 | 2010-11-10 | Genzyme Corp | Methods of augmenting or repairing soft tissue |
US20090117188A1 (en) * | 2007-11-02 | 2009-05-07 | Gershkovich Julia B | Methods of Augmenting or Repairing Soft Tissue |
US20090294049A1 (en) * | 2008-06-02 | 2009-12-03 | Medtronic Vascular, Inc. | Biodegradable Adhesive Hydrogels |
US20110086014A1 (en) * | 2008-06-18 | 2011-04-14 | Ishay Attar | Method for enzymatic cross-linking of a protein |
US8703117B2 (en) | 2008-06-18 | 2014-04-22 | Lifebond Ltd. | Cross-linked compositions |
US8367388B2 (en) | 2008-06-18 | 2013-02-05 | Lifebond Ltd. | Cross-linked compositions |
US20110110882A1 (en) * | 2008-06-18 | 2011-05-12 | Orahn Preiss-Bloom | Cross-linked compositions |
US9044456B2 (en) | 2008-06-18 | 2015-06-02 | Lifebond Ltd. | Cross-linked compositions |
US20110112573A1 (en) * | 2008-06-18 | 2011-05-12 | Orahn Preiss Bloom | Methods and devices for use with sealants |
US8409606B2 (en) | 2009-02-12 | 2013-04-02 | Incept, Llc | Drug delivery through hydrogel plugs |
US8563027B2 (en) | 2009-02-12 | 2013-10-22 | Incept, Llc | Drug delivery through hydrogel plugs |
US8962764B2 (en) | 2009-03-27 | 2015-02-24 | Carnegie Mellon University | Preparation of functional star macromolecules |
US20130304177A1 (en) * | 2009-05-20 | 2013-11-14 | Maria Palasis | Drug Eluting Medical Implant |
US10617796B2 (en) | 2009-05-20 | 2020-04-14 | Lyra Therapeutics, Inc. | Drug eluting medical implant |
US8540765B2 (en) * | 2009-05-20 | 2013-09-24 | 480 Biomedical, Inc. | Medical implant |
US20120143300A1 (en) * | 2009-05-20 | 2012-06-07 | Arsenal Medical | Medical implant |
US20130317600A1 (en) * | 2009-05-20 | 2013-11-28 | Maria Palasis | Drug eluting medical implant |
US9278016B2 (en) | 2009-05-20 | 2016-03-08 | 480 Biomedical, Inc. | Medical implant |
US8992601B2 (en) | 2009-05-20 | 2015-03-31 | 480 Biomedical, Inc. | Medical implants |
US9309347B2 (en) | 2009-05-20 | 2016-04-12 | Biomedical, Inc. | Bioresorbable thermoset polyester/urethane elastomers |
US10568994B2 (en) | 2009-05-20 | 2020-02-25 | 480 Biomedical Inc. | Drug-eluting medical implants |
US9155638B2 (en) * | 2009-05-20 | 2015-10-13 | 480 Biomedical, Inc. | Drug eluting medical implant |
US9737647B2 (en) | 2009-05-20 | 2017-08-22 | Arsenal Medical, Inc. | Drug-eluting medical implants |
US8888840B2 (en) * | 2009-05-20 | 2014-11-18 | Boston Scientific Scimed, Inc. | Drug eluting medical implant |
US11160883B2 (en) | 2009-12-15 | 2021-11-02 | Incept, Llc | Echolucent implant composition and methods |
US10272164B2 (en) | 2009-12-15 | 2019-04-30 | Incept, Llc | Implants and biodegradable tissue markers |
US11083802B2 (en) | 2009-12-15 | 2021-08-10 | Incept, Llc | Echolucent implant compositions and methods |
US9669117B2 (en) | 2009-12-15 | 2017-06-06 | Incept, Llc | Implants and biodegradable tissue markers |
US20110142936A1 (en) * | 2009-12-15 | 2011-06-16 | Patrick Campbell | Implants and biodegradable fiducial markers |
US10786581B2 (en) | 2009-12-15 | 2020-09-29 | Incept, Llc | Implants and biodegradable tissue markers |
US11154624B2 (en) | 2009-12-15 | 2021-10-26 | Incept, Llc | Echolucent implant compositions and methods |
US11786612B2 (en) | 2009-12-15 | 2023-10-17 | Incept, Llc | Implant and biodegradable tissue marker compositions and methods |
US8852646B2 (en) | 2009-12-15 | 2014-10-07 | Incept, Llc | Particulate implants and biodegradable fiducial markers |
US9308283B2 (en) | 2009-12-15 | 2016-04-12 | Incept, Llc | Implants and biodegradable fiducial markers |
US8383161B2 (en) | 2009-12-15 | 2013-02-26 | Incept, Llc | Radioopaque covalently crosslinked hydrogel particle implants |
US10202585B2 (en) | 2009-12-22 | 2019-02-12 | Lifebond Ltd | Modification of enzymatic crosslinkers for controlling properties of crosslinked matrices |
US9066991B2 (en) | 2009-12-22 | 2015-06-30 | Lifebond Ltd. | Modification of enzymatic crosslinkers for controlling properties of crosslinked matrices |
US9232805B2 (en) | 2010-06-29 | 2016-01-12 | Biocure, Inc. | In-situ forming hydrogel wound dressings containing antimicrobial agents |
US8961544B2 (en) | 2010-08-05 | 2015-02-24 | Lifebond Ltd. | Dry composition wound dressings and adhesives comprising gelatin and transglutaminase in a cross-linked matrix |
US8961501B2 (en) | 2010-09-17 | 2015-02-24 | Incept, Llc | Method for applying flowable hydrogels to a cornea |
US9493606B2 (en) * | 2010-09-21 | 2016-11-15 | Total Research & Technology Feluy | One-step, one-pot process for preparing multiblock and gradient copolymer |
US20140148558A1 (en) * | 2010-09-21 | 2014-05-29 | Centre National De La Recherche Scientifique(Cnrs) | One-step, one-pot process for preparing multiblock and gradient copolymer |
US9644042B2 (en) | 2010-12-17 | 2017-05-09 | Carnegie Mellon University | Electrochemically mediated atom transfer radical polymerization |
US10072042B2 (en) | 2011-08-22 | 2018-09-11 | Carnegie Mellon University | Atom transfer radical polymerization under biologically compatible conditions |
US10226417B2 (en) | 2011-09-16 | 2019-03-12 | Peter Jarrett | Drug delivery systems and applications |
US11890343B2 (en) | 2011-12-05 | 2024-02-06 | Incept, Llc | Medical organogel processes and compositions |
US10905765B2 (en) | 2011-12-05 | 2021-02-02 | Incept, Llc | Medical organogel processes and compositions |
US9205150B2 (en) | 2011-12-05 | 2015-12-08 | Incept, Llc | Medical organogel processes and compositions |
US9533297B2 (en) | 2012-02-23 | 2017-01-03 | Carnegie Mellon University | Ligands designed to provide highly active catalyst complexes |
US20170274102A1 (en) * | 2014-08-15 | 2017-09-28 | The Johns Hopkins University | Post-surgical imaging marker |
US11191853B2 (en) * | 2014-08-15 | 2021-12-07 | The Johns Hopkins University | Post-surgical imaging marker |
US9982070B2 (en) | 2015-01-12 | 2018-05-29 | Carnegie Mellon University | Aqueous ATRP in the presence of an activator regenerator |
US10617563B2 (en) | 2015-07-22 | 2020-04-14 | Incept, Llc | Coated implants |
US10335124B1 (en) | 2016-02-29 | 2019-07-02 | Devicor Medical Products, Inc. | Marker delivery device with adaptor for biopsy site marking and method of use thereof |
US11794156B2 (en) | 2016-06-30 | 2023-10-24 | Devicor Medical Products, Inc. | Marker having enhanced ultrasound visibility and method of manufacturing the same |
US10610841B1 (en) | 2016-06-30 | 2020-04-07 | Devicor Medical Products, Inc. | Marker having enhanced ultrasound visibility and method of manufacturing the same |
US11174325B2 (en) | 2017-01-12 | 2021-11-16 | Carnegie Mellon University | Surfactant assisted formation of a catalyst complex for emulsion atom transfer radical polymerization processes |
US11090132B2 (en) | 2017-09-15 | 2021-08-17 | Devicor Medical Products, Inc. | Method for manufacturing marker with aerated hydrogel |
US11191610B2 (en) | 2017-09-26 | 2021-12-07 | Devicor Medical Products, Inc. | Biopsy site marker with microsphere coating |
WO2019067441A1 (en) | 2017-09-26 | 2019-04-04 | Devicor Medical Products, Inc. | Biopsy site marker with microsphere coating |
US12065539B2 (en) | 2018-04-19 | 2024-08-20 | Poly-Med, Inc. | Macromers and compositions for photocuring processes |
EP3781384A4 (en) * | 2018-04-19 | 2022-01-26 | Poly-Med Inc. | Macromers and compositions for photocuring processes |
US11639416B2 (en) | 2018-04-19 | 2023-05-02 | Poly-Med, Inc. | Macromers and compositions for photocuring processes |
US11998654B2 (en) | 2018-07-12 | 2024-06-04 | Bard Shannon Limited | Securing implants and medical devices |
US11447602B2 (en) | 2018-09-26 | 2022-09-20 | Sofradim Production | Biodegradable triblock copolymers and implantable medical devices made therefrom |
EP4193932A1 (en) | 2018-12-10 | 2023-06-14 | Devicor Medical Products, Inc. | Biopsy system with end deploy needle |
WO2020123350A1 (en) | 2018-12-10 | 2020-06-18 | Devicor Medical Products, Inc. | Biopsy system with end deploy needle |
WO2020131654A1 (en) | 2018-12-17 | 2020-06-25 | Devicor Medical Products, Inc. | Apparatus for delivering biopsy cavity marker |
WO2020168026A1 (en) | 2019-02-15 | 2020-08-20 | Devicor Medical Products, Inc. | Marker delivery device with sterile guide |
US12029399B2 (en) | 2019-02-15 | 2024-07-09 | Devicor Medical Products, Inc. | Marker delivery device with sterile guide |
EP4278985A2 (en) | 2019-05-30 | 2023-11-22 | Devicor Medical Products, Inc. | Biopsy site marker for limited migration |
WO2020243386A1 (en) | 2019-05-30 | 2020-12-03 | Devicor Medical Products, Inc. | Shape memory marker deployment device |
WO2020243474A1 (en) | 2019-05-30 | 2020-12-03 | Devicor Medical Products, Inc. | Biopsy site marker for limited migration |
WO2020243470A1 (en) | 2019-05-30 | 2020-12-03 | Devicor Medical Products, Inc. | Methods and apparatus for direct marking |
EP4279015A2 (en) | 2019-05-30 | 2023-11-22 | Devicor Medical Products, Inc. | Apparatus for direct marking |
WO2021146367A2 (en) | 2020-01-15 | 2021-07-22 | Devicor Medical Products, Inc. | Marker delivery device with push rod having actuation features |
WO2021188479A1 (en) | 2020-03-17 | 2021-09-23 | Devicor Medical Products, Inc. | Non-migrating biopsy site identifiers |
WO2021188481A2 (en) | 2020-03-17 | 2021-09-23 | Devicor Medical Products, Inc. | Biopsy site markers with non-migration features |
WO2022119911A1 (en) | 2020-12-02 | 2022-06-09 | Devicor Medical Products, Inc. | A marker delivery device configured to decouple plunger and push rod |
WO2023215090A1 (en) | 2022-05-03 | 2023-11-09 | Devicor Medical Products, Inc. | Biopsy site marker with increased visualization and non-migration features |
WO2023249760A1 (en) | 2022-06-23 | 2023-12-28 | Devicor Medical Products, Inc. | Biopsy site marker with expandable mesh |
WO2024039561A1 (en) | 2022-08-16 | 2024-02-22 | Devicor Medical Products, Inc. | Biopsy site marker having movable portions |
WO2024039560A1 (en) | 2022-08-16 | 2024-02-22 | Devicor Medical Products, Inc. | Biopsy site marker having expandable portion |
WO2024086055A1 (en) | 2022-10-21 | 2024-04-25 | Devicor Medical Products, Inc. | Biopsy device with end deployment for marker delivery |
DE102023128960A1 (en) | 2022-10-21 | 2024-05-02 | Devicor Medical Products, Inc. | FLUID DEPLOYMENT MECHANISM FOR BIOPSY SITE MARKER |
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ZA978537B (en) | 1998-05-12 |
US6177095B1 (en) | 2001-01-23 |
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